Lipidology doi: 10.3390/lipidology3020020

Authors: Ola A. Al-Ewaidat Moawiah M. Naffaa

Lipids are commonly viewed as membrane components, energy sources, or precursors of signaling molecules, yet accumulating evidence indicates a broader role in determining the functional state of cells. In this review, we present an integrative cross-domain synthesis in which lipids are discussed as important modulators of cellular functional state across inflammation, tissue regeneration, and chronic disease. We discuss how membrane lipid composition shapes receptor and ion-channel signaling, how bioactive lipid mediators govern the balance between inflammatory initiation and resolution, and how lipid metabolism regulates stem-cell quiescence, activation, and regenerative capacity. We integrate these mechanisms to show how disruption of lipid-regulated processes may bias tissues toward persistent inflammation, impaired repair, and disease progression in conditions such as rheumatic disorders, fibrosis, and neurodegeneration. Depending on context, such lipid alterations may function as causal contributors, permissive conditions, or downstream signatures of pathological state transitions. Finally, we consider how pharmacological and nutritional modulation of lipid pathways may influence cellular states, while emphasizing that the main contribution of this review is a conceptual state-transition framework that links membrane architecture, mediator balance, and lipid metabolic flux across inflammation, regeneration, and chronic disease.

Lipidology doi: 10.3390/lipidology3020019

Authors: Jean Kaique Valentim Alexander Alexandre de Almeida Helder Freitas de Oliveira Rodrigo Garófallo Garcia

Lipids play a central role in poultry nutrition by modulating energy utilization, nutrient digestibility, and metabolic processes related to lipid absorption and deposition. This review synthesizes current knowledge on the main dietary lipid sources used in poultry nutrition and their effects on performance, lipid metabolism, and egg yolk fatty acid composition. Conventional lipid sources, including vegetable oils and animal fats, differ in fatty acid profile, degree of saturation, and digestibility, which directly influence metabolic efficiency and productive responses. In addition, the strategic use of lipid sources enables the modulation of fatty acid profiles in poultry products, particularly through the enrichment of polyunsaturated fatty acids such as omega-3. These effects are associated with mechanisms involving lipid digestion, absorption, and hepatic lipoprotein synthesis, which regulate fatty acid deposition in tissues and egg yolks. However, responses to dietary lipids are influenced by factors such as inclusion level, oxidative stability, and lipid composition. Overall, dietary lipid manipulation represents an effective strategy to optimize production efficiency and enhance the nutritional quality of poultry-derived foods.

Lipidology doi: 10.3390/lipidology3020018

Authors: Alexandra Stiegler Michaela Schirato Ionela-Mariana Nagelreiter Christina Bauer Sarah Jelleschitz Christopher Kremslehner Christos C. Zouboulis Dóra Kovács Kinga Lénárt Miriam Maiellaro Emanuela Camera Dániel Törőcsik Florian Gruber

Background/Objectives: Sebocytes, the primary cell type in sebaceous glands (SGs), produce a lipid mixture called sebum that is released onto the skin surface and is required for skin homeostasis. The lipid receptor Peroxisome Proliferator-Activated Receptor gamma (PPARγ) regulates sebocyte proliferation and lipid synthesis and is involved in acne development. As inhibition of PPARγ has been shown to reduce insulin-induced lipogenesis and Akt/mTOR signalling in SZ95 sebocytes, we here investigated the effects of PPARγ deletion on lipid homeostasis and autophagic stress responses and how the secretomes affect dermal fibroblasts. Methods: SZ95 sebocytes wildtype (WT) and PPARγ knockout (KO) were shifted to low serum and EGF-deficient conditions permissive for autophagy. Untargeted and targeted HPLC-MS/MS analyses were used to analyze native and oxidized lipids, respectively. Protein levels of LC3I/II and p62 were assessed using immunoblots and immunofluorescence microscopy to investigate the autophagic flux. Dermal fibroblasts were exposed to conditioned media. Results: In low serum culture media, KO SZ95 sebocytes displayed significantly altered levels of 23 lipid classes. We observed a significant increase in ether-linked fatty acids as components of complex lipids and detected elevated levels of phospholipid hydroperoxides and aldehydolipids in the KO sebocytes. KO SZ95 sebocytes failed to show the typical responses to lipoxidative stress, such as elevated p62 crosslinking or inclusion body formation, and had reduced LC3II/I ratios as compared to WT cells. PPARγ KO conditioned media promoted a trend towards an inflammatory fibroblast phenotype. Conclusions: These findings suggest that PPARγ in sebocytes may alter the lipidome, elevate redox stress, and affect the autophagic machinery, which could cause accumulation of oxidized lipids and other potentially harmful compounds in sebocytes.

Lipidology doi: 10.3390/lipidology3020017

Authors: Svitlana Miros Svitlana Bilokon Yiting Han Ronald Halim

Background/Objectives: Microalgae are gaining increasing attention as sustainable sources of dietary lipids and other bioactive compounds; however, the relationship between microalgae lipid composition and physiological outcomes in vivo remains insufficiently understood. This study aimed to characterize antioxidant activity, total lipid content and fatty acid (FA) profiles of selected freshwater microalgae and to evaluate their dietary impact using Drosophila melanogaster as a whole-organism model. Methods: Four freshwater microalgal species (Chlorella vulgaris, Nannochloris limnetica, Scenedesmus communis, and Tetradesmus obliquus) were cultivated separately in 3N-BBM+V medium under controlled laboratory conditions. DPPH, FRAP and TPC were measured in microalgae methanolic extracts. Total lipids were extracted using a modified Breuer method and quantified gravimetrically. FA profiles were determined as fatty acid methyl esters by GC-FID. Freeze-dried microalgal biomass (3 mg/mL) was incorporated into standard D. melanogaster diet. Lifespan and body mass were assessed separately in females and males, as well as fecundity in general. Results: Total lipid content ranged from 17.3% to 28.1% of dry weight, with FA profiles dominated by C16 saturated, monounsaturated (omega-9), and omega-6 polyunsaturated fatty acids. Correlation analysis indicates that antioxidant properties of the studied microalgae are more closely linked to lipid fractions than to phenolic content. Dietary supplementation with microalgal biomass of three out of four microalgal species significantly extended median lifespan, particularly in males, without adverse effects on body mass or fecundity. Conclusions: These findings indicate that freshwater microalgae can serve as a physiologically safe dietary lipid source. D. melanogaster represents a suitable in vivo model for screening the nutritional potential of microalgal lipids.

Lipidology doi: 10.3390/lipidology3020016

Authors: Priya Rathor Ashutosh K. Tiwari Damodara N. Kommi Ratnasekhar CH

Micro- and nanoplastics (MNPs) are increasingly recognized as frequent environmental pollutants with growing evidence of tissue-specific lipid disruption in exposed organisms. MNP exposure is unavoidable and has attracted global attention due to its potential public health and ecological security risks. Unlike earlier studies that emphasize oxidative stress and inflammation, recent findings show that lipids are among the earliest and most sensitive molecular targets of MNP exposure. Lipidomics investigations across animal models reveal consistent patterns of lipidome remodeling, including altered phospholipid composition, disrupted sphingolipid balance, increased neutral-lipid storage, and mitochondrial lipid damage in metabolically active tissues such as the liver, kidney, lung, adipose tissue, and brain. Mechanistically, MNPs perturb membrane bilayer organization, induce MUFA and PUFA peroxidation, and destabilize lysosomal and mitochondrial function. These alterations trigger cardiolipin oxidation, ceramide accumulation, lipid droplet biogenesis, and impaired lipophagy, which collectively promote metabolic stress, energy imbalance, and neurotoxic or hepatotoxic phenotypes. Despite the growing number of tissue-specific studies, a major gap remains in understanding systemic MNP toxicity. The present review uniquely emphasizes tissue-resolved lipidomic signatures to identify convergent pathways of lipid disruption and proposes a conceptual framework, the “Lipid–Stress Axis”, to explain how localized lipidome perturbations may propagate into broader physiological dysfunction. By integrating lipidomics with metabolomics, imaging, and systems-biology approaches, we highlight key lipid-based biomarkers, mechanistic insights, and research needs essential for improving risk assessment and developing mitigation strategies against MNP-induced lipid dysregulation.

Lipidology doi: 10.3390/lipidology3020015

Authors: Viren Jadeja Shiyu Ma Heping Zhou

Background/Objectives: Palmitic acid (PA), the most abundant saturated fatty acid in circulation, is elevated in obese individuals and has been implicated in promoting inflammation. However, its effects on inflammatory cytokine production in microglial cells and the involvement of cell surface receptors remain poorly characterized. Methods: In this study, we treated BV2 murine microglial cells with 200 µM PA or bovine serum albumin (BSA) control for 24 h and assessed IL-1β expression using semi-quantitative RT-PCR and/or ELISA. The roles of toll-like receptor (TLR)-2, TLR-4, G-protein-coupled receptor (GPR) 40, and GPR120 were investigated using siRNA knockdown and/or pharmacological inhibition. Results: Our studies found that PA treatment significantly increased IL-1β production as well as the mRNA expression of TLR-2, TLR-4, GPR40, and GPR120 compared to BSA controls. IL-1β expression correlated positively with TLR-2, TLR-4, and GPR40 levels. RNAi silencing of TLR-2, TLR-4, or GPR40 substantially diminished IL-1β expression in cells exposed to both BSA and PA. In contrast, neither RNAi silencing nor pharmacological inhibition of GPR120 suppressed IL-1β expression, suggesting that GPR120 may not mediate PA-induced inflammation. Conclusions: Our studies suggest that PA-induced production of IL-1β may be mediated via TLR-2, TLR-4, and GPR40, and that these cell surface receptors may serve as important molecular links between saturated fatty acids (SFAs) and neuroinflammation.

Lipidology doi: 10.3390/lipidology3020014

Authors: Dimitrios Kalompatsios Vassilis Athanasiadis Athanasia Giannakopoulou Martha Mantiniotou Eleni Bozinou Alexandros Papachatzis Stavros I. Lalas

Background/Objectives: Lipid oxidation is a major factor limiting the shelf life and nutritional quality of edible vegetable oils. Enhancing the oxidative stability of extra virgin olive oil (EVOO) through natural antioxidants is of increasing interest to both industry and consumers. This study aimed to evaluate the impact of five plant-derived essential oils (orange, lemon, black pepper, oregano, and rosemary) incorporated at three concentrations (0.5, 1, and 2% w/w) on the oxidative stability, antioxidant capacity, and bioactive compound retention of EVOO. Methods: All fortified EVOO samples were stored at 60 °C for 28 days to simulate accelerated oxidation. A positive control containing 200 ppm of butylated hydroxytoluene (BHT) was included for comparison. Oxidative stability was assessed through peroxide value, TBARS, p-anisidine value, and conjugated dienes/trienes. Tocopherols, carotenoids, and chlorophylls were quantified, while radical scavenging activity was determined using Trolox-equivalent assays. Correlation analyses were performed to explore relationships between essential oil composition and antioxidant performance. Results: Among the tested essential oils, oregano at 2% demonstrated the strongest protective effect, reducing both primary and secondary oxidation products and yielding a Totox value (34.26) close to that of the BHT-enriched control (29.86) after 28 days. Regarding long-term radical scavenging capacity, rosemary at 1% concentration provided the closest activity to BHT (402.89 vs. 536.64 μM Trolox equivalents). Both oregano and rosemary enhanced the preservation of α-tocopherol, likely due to the activity of key constituents such as carvacrol and 1,8-cineole. Conclusions: The incorporation of selected essential oils, particularly oregano and rosemary, can effectively enhance the oxidative stability and antioxidant capacity of EVOO, supporting their potential use as natural alternatives to synthetic antioxidants.

Lipidology doi: 10.3390/lipidology3020013

Authors: Gonzalo Saiz-Gonzalo Gaetan Drouin

Background: n-3 Docosapentaenoic acid (DPA; 22:5 n-3) is increasingly viewed as a distinct long-chain omega-3 fatty acid with biological activities that are not fully captured by eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA). However, progress remains limited by restricted access to high-purity DPA: most commercial sources contain DPA as a minor component, and published isolation strategies often yield only enriched mixtures or require multi-step workflows that are difficult to scale in standard laboratories. Objectives: We aimed to establish a robust, laboratory-accessible purification workflow to obtain DPA ethyl ester at high purity while preserving oxidative quality. Methods: Candidate lipid sources were screened to select an optimal DPA-containing feedstock. Oils were stabilized with antioxidants and pre-fractionated by cold crystallization (−20 °C) to reduce saturated lipids and oxidation by-products. Preparative separation used a stacked C18 flash system (15 μm + 45 μm in series) operated isocratically (methanol/water 92:8, v/v) at 120 mL/min. Fractions were analyzed by GC and iteratively reinjected to progressively enrich the DPA window. Solvent was recovered by distillation and reused. Results: Omegavie® 4020EE (5.4% n-3 DPA) was identified as the best starting material. Pretreatment eliminated detectable TBARS-derived malondialdehyde. The isocratic purification-loop strategy produced tens of grams of DPA ethyl ester at >98% purity (GC–FID) defined as n-3 DPA area% of total identified fatty acid methyl esters by GC–FID, with per-cycle DPA recovery of 91–95%, overall recovery of 76% from the starting DPA content, and >90% solvent recycling. The workflow is scalable at the gram-to-tens-of-grams level for research laboratories, although solvent burden and column maintenance remain practical constraints for larger-scale implementation. Identity and purity were confirmed by GC–MS and ^1H NMR, and oxidation indices remained low (peroxide value < 0.2 meq/kg; p-anisidine < 3). Conclusions: This scalable, solvent-conscious protocol enables reliable access to high-purity DPA and should be adaptable to other low-abundance polyunsaturated fatty acids.

Lipidology doi: 10.3390/lipidology3020012

Authors: Giulia Pecora Camilla Mancini Francesca Fabretti Aloima Yera Sara Cecchini Eleonora Pica Flaminia Russo Virginia Zamponi Rossella Mazzilli Francesca Belleudi Maria Rosaria Ricciardi Francesco Panzuto Antongiulio Faggiano

Background/Objectives: Metabolic alterations, including dyslipidemia, may influence tumor biology and treatment outcomes in neuroendocrine tumors. However, the clinical relevance of dyslipidemia and lipid-lowering therapy in bronchopulmonary neuroendocrine tumors (BP-NETs) treated with somatostatin analogues (SSAs) remains poorly defined. This translational proof-of-concept study evaluated progression-free survival (PFS) in patients with advanced BP-NETs receiving SSAs according to dyslipidemia and statin therapy and explored the effects of statin-SSA combination treatment in vitro. Methods: We retrospectively analyzed 24 patients with advanced well-differentiated BP-NETs treated with SSAs as first-line therapy. Fourteen patients (58.3%) had dyslipidemia, and 11 of them were receiving statins. In parallel, NCI-H727 cells were treated with atorvastatin (10 µM), lanreotide (5 or 10 µM), or their combination for 48–72 h. Cell viability, proliferation, cell death, apoptosis, DNA damage, and ATP production were assessed. Results: Median PFS was 22.5 months overall. A trend toward longer PFS was observed in non-dyslipidemic vs. dyslipidemic patients (70 vs. 36 months, p = 0.08). Among dyslipidemic patients, statin therapy was associated with a non-significant trend toward longer PFS compared with no statin therapy (36 vs. 18 months, p = 0.30). In vitro, combined atorvastatin–lanreotide treatment reduced cell viability and proliferation, increased cell death, enhanced cleaved caspase-3 and p-γH2AX expression, and reduced ATP production. Conclusions: These findings support the potential relevance of lipid metabolism modulation as an adjunct strategy in advanced BP-NETs while highlighting the need for larger prospective studies and dedicated biochemical investigation of the underlying lipid-related pathways.

Lipidology doi: 10.3390/lipidology3010011

Authors: Roberto Carlos Burini

Energy thriftiness and metabolic adaptations have had a crucial role in the emergence and spreading of the Homo lineage in the world. A higher-energy demand was required not only for the growing body mass, encephalization and human proliferation, but also for the survival adaptations to the environmental stresses. Because lean body mass lacks the energy-storage capacity required to supply the body’s demands, dedicated fat-storing cells originated. To feed such fat stores, the hominid evolution developed “meat-adaptive” genes to detect, digest and metabolize higher fat diets, and body-fat stores can be affected by lifestyle through hormonal-controlled daily energy balance. In energy surplus conditions, hypertrophy and hyperplasia of adipocytes can occur, with hypertrophic adipocyte signaling both a neo-adipocyte differentiation (leading to hyperplasia) and a local macrophage density (resident + infiltrated macrophages) for fat surplus scavenging. Adiposity-induced inflammation is caused by fat-overstored (hypertrophied) adipocytes that may operate as an overactive endocrine organ secreting an array of pro-inflammatory adipokines that, in combination with resident-macrophage activity and infiltrated blood-recruited, monocyte-derived macrophages, amplify the inflammatory process by spurting pro-inflammatory cytokines into the bloodstream. From an evolutionary perspective, obese humans represent a natural selection overexpressing the “thrifty” genes evolved for efficient food collection and fat deposition intended to help in survival in prolonged periods of famine. However, genetically speaking, obesity is a polygenic multifactorial disorder. Considering the rapidity of obesity-epidemic growth worldwide, epigenetic sets forth the key assumption of the mismatch between our human genome molded over thousands of generations, coping with the unprecedented dietary and physical conditions. Consequently, obesity would be due to our evolutionary-adapted polygenic-charge expressed by a deteriorated lifestyle characterized by high energy-dense food intake coupled with a reduction in caloric expenditure stemming from new mobility-reducing technologies. As a model of lifestyle change (LiSM), our 28-year on-going longitudinal study (“Moving for Health”) has shown effectiveness in the reduction not only of obesity but especially of its comorbidities, in a (10 week to 3 year) length-dependent LiSM. However, a disappointing progressive decrease in compliance with the study has been observed and attributed to the resistance of people to change their actual “obesogenic” lifestyle, basically represented by the individuals’ demand for labor-saving technologies and convenient, affordable, palatable foods.

Lipidology doi: 10.3390/lipidology3010010

Authors: Chui Yan Mah Xuan Yuan Aw Ngee Kiat Chua

The field of immunometabolism highlights the intricate interplay between immunity and metabolism. The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway is a central component of innate immunity that detects double-stranded DNA (dsDNA) from a range of sources, including pathogenic and host-derived DNA. It is now recognized that the cGAS-STING pathway has broad implications in a variety of human conditions including cancer, age-related diseases, and autoimmune disorders. Given the abundance and diversity of lipids across cellular compartments serving as structural components and signaling molecules, it is unsurprising that lipid metabolism influences the regulation of cGAS-STING signaling. Lipids can directly alter signaling protein dynamics through interactions within membrane compartments, while alterations in lipid metabolism can remodel multiple cell-intrinsic signaling cascades. Here, we summarize emerging concepts and recent discoveries that have advanced our understanding of how lipid metabolism and lipids regulate the cGAS-STING pathway.

Lipidology doi: 10.3390/lipidology3010009

Authors: Caroline Bachmeier Deborah A. Johnston Andrew Kassianos Karam M. Kostner Helen Tanner

Background: Familial hypercholesterolaemia (FH) is an inherited condition that substantially increases the risk of premature atherosclerotic cardiovascular disease (ASCVD). Despite effective therapies, many affected individuals remain undiagnosed. Incorporation of FH testing into newborn screening (NBS) is a potential strategy to increase detection. This study explores the attitudes of expectant parents toward NBS for FH. Methods: Expectant parents attending Obstetrics and/or Obstetric Medicine clinics at a tertiary referral centre were invited to participate in a semi-structured interview in person or via telephone. The interview explored views on screening children for FH in general, preferred timing of screening, opinions on integrating FH screening into routine NBS, acceptability of genetic testing in children and newborns, willingness to engage in family screening and any potential impact on participation in routine NBS programmes. Participants were also invited to discuss concerns and benefits. Results: All participants (n = 22) supported screening children for FH with the majority (n = 19, 86%) preferring screening during the newborn period, and all but one (n = 21, 95%) supporting adding FH to routine NBS. All participants (n = 22, 100%) considered genetic testing for FH acceptable for children, 21 (95%) considered it acceptable for newborns. All participants would partake in extended family screening and none indicated that including FH genetic testing would reduce their willingness to engage in routine NBS. Concerns raised by participants included administering lipid-lowering therapy to children and potential post-diagnosis stress and anxiety. All participants reported that a diagnosis would not affect parent–child bonding. Key perceived benefits raised by participants included early diagnosis and prevention of heart disease, family screening, and broader health system and community advantages. Conclusions: Expectant parents demonstrated strong support for FH NBS and indicated no negative impact on uptake of routine NBS. Further work is needed to address parental concerns and guide implementation strategies.

Lipidology doi: 10.3390/lipidology3010008

Authors: Aikaterini N. Tsouka Ioannis K. Koutsaliaris Constantinos Tellis Alexandros D. Tselepis

Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes low-density lipoprotein receptor degradation and thereby regulates plasma LDL cholesterol levels. Although PCSK9 is primarily produced by the liver, it has been detected in platelets; however, the origin and functional relevance of platelet-associated PCSK9 remain unclear. Methods: Washed platelets (WPs) were isolated from normolipidemic subjects. Endogenous platelet PCSK9 content was quantified by ELISA, and PCSK9 molecular forms were assessed by immunoblotting. The WPs were incubated with recombinant PCSK9 (recPCSK9), and platelet aggregation in response to arachidonic acid (AA) or thrombin (Thr) was evaluated. The effects of LDL- or HDL-bound PCSK9 on platelet aggregation were also examined. Results: Platelets from normolipidemic subjects contained measurable amounts of PCSK9 (0.84 ± 0.27 ng/mg protein), which increased to 2.91 ± 0.53 ng/mg protein following incubation with recPCSK9. Exposure to recPCSK9 significantly enhanced AA- and Thr-induced platelet aggregation. In contrast, LDL and HDL inhibited platelet aggregation independently of their PCSK9 content. Conclusions: Human platelets contain endogenous PCSK9 and can accumulate additional PCSK9 from the extracellular environment. Exogenous PCSK9 enhances platelet aggregation, supporting a potential prothrombotic role for circulating PCSK9 even in normolipidemic individuals. These findings provide new insight into the complex interplay between PCSK9, lipoproteins, and platelet function.

Lipidology doi: 10.3390/lipidology3010007

Authors: Mikhail V. Caga-Anan Nirodhi N. Dasanayaka Anusha N. Seneviratne

Atherosclerosis is a progressive cardiovascular disease characterized by lipid accumulation, oxidative stress, and inflammation within the arterial walls. Environmental pollutants, including particulate matter (PM), diesel exhaust particles (DEPs), and heavy metals, contribute directly to the initiation and progression of arterial plaques by promoting LDL oxidation, endothelial dysfunction, foam cell formation, and vascular inflammation, whilst high-density lipoprotein (HDL) provides protective effects. This review examines the mechanistic links between environmental exposures, lipid dysregulation, and plaque formation, highlighting how both gaseous and particulate pollutants and toxic and essential metals, as well as endocrine disrupting chemicals, influence atherosclerotic risk. Potential antioxidant and lifestyle interventions to mitigate these pollutant-driven effects are also discussed.

Lipidology doi: 10.3390/lipidology3010006

Authors: Smita Lata Sumira Malik Sagar Mondal Jutishna Bora Swati Priya Dinusha T Veettil Perinthottathil Sreejith

Lipids are a diverse group of hydrophobic molecules including fats, oils, phospholipids, and steroids that are vital for numerous biological functions including energy storage, cellular structure, and signaling whose composition and metabolism undergo profound transformations with age. These age-related shifts due to increased lipid peroxidation, disrupted cholesterol homeostasis, and altered membrane phospholipid content, actively contribute to progressive loss in cellular homeostasis and pathogenesis of major age-related diseases. This review explores the critical role of lipids: as master regulators of cellular signaling pathways, and as key drivers of chronic inflammation and metabolic dysfunction. Dysregulated lipid metabolism is central to cardiovascular disease which is driven by altered myocardial energy substrate utilization and lipoprotein dynamics. In neurodegenerative disorders like Alzheimer’s and Parkinson’s disease, disruptions in ceramide, cholesterol, and specialized pro-resolving lipid mediators fuel neuroinflammation and protein aggregation. Furthermore, we explore the dual role of dietary lipids, which can either exacerbate or mitigate age-related decline, highlighting the potential of personalized nutritional approaches and lipid-targeting therapeutics. By integrating the mechanisms of lipid signaling, inflammation, and metabolic regulation, this analysis highlights that lipids are not merely passive structural components but active drivers of the aging process, positioning lipid metabolism as a promising frontier for interventions aimed at promoting health span and combating age-related disease.

Lipidology doi: 10.3390/lipidology3010005

Authors: Preyangsee Dutta Dwaipayan Saha

Cardiovascular disease is the leading cause of mortality in insulin-resistant individuals, with metabolic cardiomyopathy preceding overt heart failure in a substantial proportion of patients with diabetes. Skeletal muscle accounts for approximately 40% of body mass and nearly 80% of insulin-stimulated glucose disposal, positioning it as a major determinant of systemic lipid flux. Dysregulation of lipid droplet dynamics, lipolysis, and fatty acid trafficking in skeletal muscle alters circulating lipid availability and promotes ectopic lipid deposition and mitochondrial stress in the myocardium. Intramyocellular lipid handling is governed by coordinated actions of lipid droplets, perilipin proteins (PLIN2 and PLIN3), adipose triglyceride lipase (ATGL), and diacylglycerol acyltransferases (DGAT1/2), which together regulate the rate and composition of fatty acid release into the circulation. Impaired coupling between intramyocellular lipid droplet turnover and mitochondrial oxidation in insulin-resistant muscle increases circulating free fatty acids, reducing cardiac oxidative capacity. In response, the myocardium undergoes mitochondrial lipid remodeling, including alterations in cardiolipin composition that impair cristae structure and electron transport chain efficiency. Excess lipid exposure activates apoptosis signal-regulating kinase-1 (ASK-1), promoting cardiomyocyte apoptosis and inflammatory signaling, while peroxisome proliferator-activated receptor gamma (PPARγ) modulates lipid uptake, storage, and mitochondrial oxidation in a context-dependent manner. This review integrates skeletal muscle–cardiac lipid crosstalk with ASK-1 and PPARγ signaling to define mechanisms linking peripheral insulin resistance to early myocardial dysfunction and to identify targets for intervention before irreversible cardiac remodeling develops.

Lipidology doi: 10.3390/lipidology3010004

Authors: Victoria M. Taormina Simonne Eisenhardt Matthew P. Gilbert C. Lawrence Kien Matthew E. Poynter Jana Kraft

Chronic, low-grade inflammation is a characteristic of metabolic diseases like type 2 diabetes. Despite recommendations to select low- or non-fat dairy foods over full-fat dairy foods for metabolic health, recent research suggests potential anti-inflammatory benefits of dairy fat consumption. We aimed to compare the systemic inflammatory tone (i.e., circulating inflammatory biomarker concentrations and ex vivo peripheral blood mononuclear cell inflammatory responses) of individuals with prediabetes after consuming diets with full-fat (3.25%) or non-fat yogurt. We hypothesized that short-term consumption of three daily full-fat yogurt servings beneficially affects inflammatory tone. Thirteen participants aged 45–75 years completed an eight-week randomized, double-masked, controlled crossover study. The two, three-week experimental diets comprised three daily servings of full-fat or non-fat yogurt and were each preceded by a one-week run-in diet. Following each diet, circulating inflammatory biomarkers and cytokine concentrations in the supernatants of peripheral blood mononuclear cells under control or lipopolysaccharide-stimulated conditions were measured. Compared with non-fat yogurt intake, circulating immature granulocyte concentrations were lower following full-fat yogurt intake, but there were no other differences in leukocyte concentrations. Circulating concentrations of cytokines or other inflammatory markers did not differ by diet. Cell supernatant interleukin-1β concentrations were lower following the full-fat yogurt diet under unstimulated conditions but were not different between diets under stimulated conditions. There were no differences by diet in supernatant concentrations of other cytokines under unstimulated or stimulated conditions. Together, minimal differences in inflammatory tone were observed following the short-term consumption of three daily servings of full-fat or non-fat yogurt in individuals with prediabetes.

Lipidology doi: 10.3390/lipidology3010003

Authors: Johanna W. Schubarth Jenny Leopold Kathrin M. Engel Jürgen Schiller

Thin-layer chromatography (TLC) remains a widely used, cost-effective and convenient method to separate small molecules, particularly in the field of natural products and (phospho)lipids. Despite advances in chromatographic methods such as high-performance liquid chromatography (HPLC), TLC retains several advantages, including simplicity and accessibility. However, a critical step is the visualization of the separated lipids on the TLC plate. Although the majority of the regularly used methods were established decades ago, there are still a number of potential pitfalls and widely unknown aspects. This review provides a concise overview about commonly used stationary phases and the solvent systems in TLC analysis of lipids. The main focus is on visualization techniques, spanning from non-specific, destructive (charring by semi-concentrated acids) to specific, non-destructive approaches (e.g., exposition to iodine to monitor unsaturated lipids). The advantages and disadvantages of the different methods will be critically discussed and frequently occurring problems highlighted. Furthermore, the combination of TLC with mass spectrometry (MS) detection will be introduced, covering both extraction-based electrospray ionization MS techniques as well as desorption techniques such as matrix-assisted laser desorption/ionization MS. MS detection, while generally more sensitive and offering molecular specificity, introduces higher technical and financial requirements compared to conventional staining. Nonetheless, the combination of TLC with MS holds significant potential for enhancing lipidomic workflows, particularly in complex biological samples.

Lipidology doi: 10.3390/lipidology3010002

Authors: Mara Lastretti Lorenzo Campedelli Tiziano Scarparo Sabina Spagna Andrea Cicoli Gavino Faa Ettore D’Aleo

Background: In recent decades, interest has grown in the link between lipid metabolism and mental health. Omega-3 fatty acids (EPA and DHA) play a crucial role in brain function, neuroplasticity, and emotional regulation. Deficiency or an imbalanced omega-6/omega-3 ratio, typical of Western diets, has been associated with an increased risk of mood disorders, such as major depression and bipolar disorder. Objective: This review critically synthesizes neurobiological and clinical evidence on the role of omega-3s in mood disorders, assessing mechanisms, randomized controlled trials, and meta-analyses, with a focus on inflammatory biomarkers and their integration into a personalized psychiatry framework. Methods: A narrative review of epidemiological studies, randomized controlled trials (RCTs), meta-analyses, and experimental research was conducted, evaluating mechanistic pathways (synaptic, inflammatory, neuroplastic, and redox) and clinical moderators (particularly inflammatory markers and dietary lipid profiles). Results: Consistent evidence indicates that EPA-enriched formulations (≥60%) exert antidepressant effects, particularly in patients with elevated inflammatory markers (CRP, IL-6, TNF-α). In contrast, DHA-only preparations show limited efficacy, and outcomes vary depending on dietary omega-6/omega-3 balance. However, the literature remains heterogeneous in design, sample size, and biomarker stratification, which limits generalizability and contributes to conflicting findings across studies. Conclusions: While omega-3 fatty acids represent promising adjunctive interventions for mood disorders, methodological weaknesses and inconsistent formulations hinder definitive conclusions. Future research should prioritize biomarker-guided, precision-based approaches to clarify therapeutic efficacy and optimize clinical use.

Lipidology doi: 10.3390/lipidology3010001

Authors: Jacob J. Adler

Background/Objectives: Long-chain fatty acids induce lipid droplet formation in several cell types including cancer cells. These lipid droplets have been shown to accumulate in various cancers and are dysregulated in many pathologies. Thus, this study was designed to examine the many unique long-chain fatty acids and their abilities to induce lipid droplet formation in cancer cells. Methods: HeLa human cervical cancer cells were incubated with individual fatty acids and live-stained for lipid droplets. This study analyzed four saturated, four monounsaturated, and nine polyunsaturated (4 omega-3, 4 omega-6, and 1 omega-9) fatty acids. This diversity of fatty acids was chosen to highlight any important non-uniform differences in the regulation of lipid droplet formation by unsaturated fatty acids. The area of the lipid droplets and the number of lipid droplets per cell were measured and compared between the different fatty acid conditions. Results: Unsaturated fatty acids induced lipid droplets differently compared to saturated fatty acids. Further, an inverse relationship was established between average area of lipid droplets and the average number of lipid droplets per cell. Finally, two perilipin genes (PLIN1/2) involved in lipid droplet formation were shown to have significantly higher expression with the two polyunsaturated fatty acids (alpha- and gamma-linolenic acid) versus the saturated fatty acid (stearic acid) condition. Conclusions: Together, different fatty acids produce structurally different lipid droplets. It will be important to further investigate the biochemistry and mechanistic differences in the formation of these lipid droplets under these specific long-chain fatty acid conditions.

Lipidology doi: 10.3390/lipidology2040025

Authors: Juan Sabín Andrea Santisteban-Veiga Alba Costa-Santos Óscar Abelenda Vicente Domínguez-Arca

Liposomes started to be studied for drug delivery in 1970s, taking advantage of their ability to encapsulate hydrophilic and hydrophobic drugs using biodegradable and biocompatible molecules. Nowadays, they remain one of the most promising strategies for drug delivery not only in cancer treatment but also in gene therapies and vaccines. The design and development of liposomal systems have evolved significantly over the past decades, moving from conventional formulations to advanced, stimulus-responsive, and multifunctional nanocarriers. Analogous to the myth of the Trojan Horse, liposomes must mislead the host immune system to reach the interior of cancer cells in order to deliver the therapeutic payload. There are many barriers that liposomes have to overcome to circulate through the bloodstream and specifically target cancer cells without damaging other tissues. Crucial parameters such as lipid composition, particle size, zeta potential, and PEGylation have been systematically optimized to enhance pharmacokinetics and biodistribution and to improve delivery efficiency. Furthermore, conjugation with antibodies, peptides, or small molecules has enabled active targeting, while stimuli such as pH, temperature, and enzymatic activity have been exploited for controlled drug release within the tumor microenvironment. Such innovations have laid the groundwork for translating liposomal formulations from the bench to clinical applications. In this paper, we evaluate the physicochemical features of liposomal design that underpin their suitability and efficacy for anticancer drug delivery. We aimed to focus on two main aspects: conducting an exhaustive review of the physicochemical parameters of liposomal drugs that have already been approved by regulatory agencies, while maintaining a pedagogical approach when explaining the key design parameters for the optimal design of liposomes in oncology in detail.

Lipidology doi: 10.3390/lipidology2040024

Authors: Emily C. Youngmark Jana Kraft

Milk fatty acid (FA) synthesis and enteric methanogenesis share common biochemical pathways related to rumen fermentation patterns and microbial volatile FA production. The FA profile of milk is known to correlate with methane (CH4) emissions; thus, FA profiling has been proposed as an indirect method to predict CH4 emissions from dairy cattle. This study aimed to (1) investigate the milk FA profiles of Holstein cows to identify candidate biomarkers for predicting CH4 output (g/d), CH4 yield (g/kg dry matter intake), and CH4 intensity (g/kg energy-corrected milk), and (2) develop and compare regression models predicting CH4 emissions. Forty-eight cows, fed industry standard diets, were enrolled in an exploratory trial. Milk samples and CH4 measurements were collected thrice per day, and intake was recorded daily. Milk lipids were extracted, transesterified, and subsequently analyzed via gas–liquid chromatography. Three penalized regression models were compared for predicting CH4 emission metrics using milk FAs and management variables. Methane emission metrics corelated positively with short- and medium-chain FAs, polyunsaturated FAs, and branched-chain FAs, while monounsaturated FAs correlated negatively. Notably, this study observed novel correlations between 11-cyclohexyl-11:0; and 20:3 c5,c8,c11 and CH4 metrics (|r| = 0.58–0.79). Across all CH4 metrics, the models demonstrated high predictive accuracy (R2 = 0.71–0.87; concordance correlation coefficient = 0.83–0.93). The findings of this study indicate that milk FA profiling may be an effective method to detect CH4 emissions from cows fed industry standard diets and highlight the need for further refinement of prediction models.

Lipidology doi: 10.3390/lipidology2040023

Authors: Owen Miller Christopher J. Scarlett Taiwo O. Akanbi

Background/objectives: Plant-based meat analogues (PBMAs) are designed to mimic meat products and to be cooked under similar conditions by consumers. There have been few studies into the lipid stability of PBMAs, and no published studies have investigated the effect of cooking on the lipid stability of PBMAs. Methods: This study analysed the effect of recommended cooking conditions on the lipid oxidation of three commercial chicken schnitzel PBMAs with differing fatty acid composition. Fatty acids and lipid classes were analysed using gas chromatography (GC) and capillary chromatography (Iatroscan) with flame ionisation detectors, respectively. Lipid oxidation was analysed using multiple tests, including peroxide value (POV), p-Anisidine value, acid value, and thiobarbituric acid reactive substance (TBARS) tests, which then allowed for the total oxidation (TOTOX) to be calculated. Results: Fatty acid analysis by GC showed different levels of saturated and unsaturated fatty acid contents in all PBMAs, with oleic acid (C18:1) being the most abundant (product A = 52%; product B = 62%; product C = 37%). Meanwhile, lipid class analyses by Iatroscan revealed that the oils used in the PBMAs were composed of triacylglycerol (TAG), which remained intact after cooking. Lipid oxidation tests showed no major increases between the raw and cooked PBMA. Also, the TOTOX values for each product did not increase significantly (p < 0.05) due to cooking (TOTOX values for raw/cooked product A = 9.36/9.99; product B = 5.88/6.19; product C = 11.31/11.92), suggesting a broad stability of the lipids. Conclusions: Therefore, if the on-package cooking instructions are followed for these three PBMA products, their lipid oxidation levels remain within safe limits.

Lipidology doi: 10.3390/lipidology2040022

Authors: Alessandra Errigo Maria Pina Dore Elettra Merola Giovanni Mario Pes

Background: Familial hypercholesterolemia (FH) is a monogenic disorder causing markedly elevated low-density lipoprotein cholesterol (LDL-C) and premature atherosclerosis. Glucose-6-phosphate dehydrogenase (G6PD) is a key enzyme in antioxidant defense via NADPH production. G6PD deficiency, an X-linked disorder impairing redox homeostasis, may contribute to cardiovascular disease (CVD) risk. This study examined whether G6PD deficiency increases CVD risk in FH patients. Methods: We retrospectively analyzed 217 FH patients. Clinical data included demographics, lipid profiles, G6PD status, and atherosclerotic CVD outcomes (coronary, cerebrovascular, or peripheral arterial disease). In a subset, FH was confirmed by LDLR gene sequencing, and G6PD Mediterranean and Seattle variants were genotyped. Cumulative CVD prevalence was compared between G6PD-deficient and G6PD-normal FH patients. Multivariable logistic regression was adjusted for age, sex, body mass index, high blood pressure, and smoking. Results: Participants (mean age 47 years, 60% female) had markedly elevated LDL-C (mean 292 mg/dL at diagnosis). Atherosclerotic CVD was present in 119 (55%) patients. G6PD-deficient FH patients had a significantly higher CVD prevalence than those with normal G6PD activity (77.4% vs. 39.8%, p < 0.0001). LDL-C levels were higher in the G6PD-deficient group than in the non-deficient group, and this difference reached statistical significance in the univariate analysis. In the multivariable analysis, G6PD deficiency remained an independent CVD predictor (adjusted OR 3.57, 95% CI 1.30–9.83) after controlling for conventional risk factors. Conclusions: In FH, hereditary G6PD deficiency is associated with a markedly increased risk of atherosclerotic CVD. A pro-oxidative state in G6PD-deficient FH patients may play a role in premature atherogenesis. G6PD status may represent a cardiovascular risk modifier in FH, warranting further research into underlying mechanisms and targeted management.

Lipidology doi: 10.3390/lipidology2040021

Authors: Viviane de Souza Silva Luna Valentina Angulo Arias Franciane Colares Souza Usberti Rafael Augustus de Oliveira Farayde Matta Fakhouri

This systematic review examines the impact of vegetable oil consumption, such as extra virgin olive, olive, soybean, palm olein, corn, and camellia seed oils, on both human and animal health, alongside factors influencing oil quality and safety. A variety of studies were included, such as clinical trials, cohort studies, animal experiments, and reports on production methods and contamination (polycyclic aromatic hydrocarbons (PAHs) and heavy metals). The literature search was performed in scientific databases indexed up to September 2025, and risk of bias was assessed using specific tools appropriate for each study design. The findings suggest that, among the oils studied, extra virgin olive oil showed the most consistent benefits, including improvements in endothelial function, lipid profiles, weight management, and reduced mortality in humans. Animal studies corroborate hepatoprotective effects and weight regulation benefits. Oil quality is influenced by genetic, environmental, and technological factors, including cultivar selection, pollination, post-harvest handling, and extraction techniques (cold, hot, DIC, MFA, encapsulation) and refining processes, which can affect both nutritional benefits and contaminant levels. Although contaminants such as PAHs and heavy metals (Cd, Pb, As) are generally below regulatory thresholds, some contexts may present health risks. High-quality vegetable oils confer cardiovascular, metabolic, and hepatic benefits. However, their contribution to public health relies on strict production practices, continuous monitoring of contaminants, and the implementation of technological innovations to ensure both safety and optimal health outcomes.

Lipidology doi: 10.3390/lipidology2040020

Authors: Stylianos Fakas Ayodeji Odunsi

ATP citrate lyase (ACL) is a highly conserved enzyme across eukaryotes that catalyzes the generation of cytosolic acetyl-CoA from citrate—a pivotal step linking central carbon metabolism to lipid biosynthesis. In the oleaginous yeast Yarrowia lipolytica, ACL is encoded by two genes, ACL1 and ACL2, forming a heteromeric complex that mirrors the multidomain architecture of the single-chain ACL enzymes found in mammals and plants. This conservation of catalytic architecture reflects a shared catalytic strategy across kingdoms, underscoring ACL’s fundamental role in metabolic integration. In Y. lipolytica, ACL is essential for directing mitochondrial citrate toward acetyl-CoA production and subsequent lipid accumulation. Yet, in contrast to well-characterized ACLs in animals and plants, the functional mechanisms and regulation of yeast ACL remain incompletely understood. A deeper understanding of ACL in Y. lipolytica offers not only evolutionary insights but also potential avenues for engineering lipid overproduction in microbial systems.

Lipidology doi: 10.3390/lipidology2040019

Authors: Zoofa Zayani Arash Matinahmadi Alireza Tavakolpournegari Seyedeh Safoora Moosavi Seyed Hesamoddin Bidooki

In the last twenty years, an increasing volume of research has characterized lipids as dynamic signaling molecules that play essential roles in various physiological and pathological processes, especially concerning chronic diseases such as cardiovascular disorders, diabetes, liver disease, neurodegeneration, cancer, obesity, diabetic and chronic kidney diseases and atherosclerosis. Dysregulation of lipid synthesis and storage, lipolysis, fatty acid oxidation, lipid signaling pathways, and organelle-specific lipid modifications, including mitochondrial phospholipid remodeling and endoplasmic reticulum stress induced by saturated fatty acids, are recognized as contributors to the initiation and progression of this pathogenesis. Concurrently with the increasing comprehension of lipid metabolism, the last decade has seen progress in the understanding of genome control, especially with non-coding RNAs (ncRNAs). MicroRNAs, long non-coding RNAs, and circular RNAs, as ncRNAs, are essential modulators of gene expression at the epigenetic, transcriptional, and post-transcriptional levels that affect a number of lipid metabolism-related processes, such as fatty acid synthesis and oxidation, cholesterol homeostasis, and lipid droplet dynamics. Therapeutically, ncRNAs hold considerable promise owing to their tissue specificity and modularity, with antisense oligonucleotides and CRISPR-based editing currently under preclinical evaluation. In this context, we review recent studies exploring the interplay between ncRNAs and the regulatory networks governing lipid metabolism, and how disruptions in these networks contribute to chronic disease. This emerging paradigm underscores the role of ncRNA–lipid metabolism interactions as central nodes in metabolic and inflammatory pathways, highlighting the need for a holistic approach to therapeutic targeting.

Lipidology doi: 10.3390/lipidology2040018

Authors: Corinne D. Mack Lily D. Quagliata Rana Baraz Sravanthi Naralashetty Suat Dervish Helen Williams Stephen C. H. Li Heather J. Medbury

Background: Dyslipidaemia promotes atherosclerotic plaque formation. Plaques that are vulnerable to rupture have a higher proportion of inflammatory (M1:CD86) macrophages in their cap. Many plaque macrophages are derived from blood monocytes which have been exposed to elevated blood lipid levels. Here, we explored whether the inflammatory state of monocyte-derived macrophages is associated with blood lipid levels and assessed whether oxidised low-density lipoprotein (oxLDL) directly induces some of the observed changes. Method: Blood was collected from 20 individuals. Lipid profiles were measured, and monocytes differentiated into macrophages. Macrophage inflammatory state was assessed by flow cytometry for phenotypic markers (e.g., CD86 and CD163) and cytokine production: TNF, IL-1β, and IL-6. Furthermore, monocytes were isolated from 6 normo-lipidaemic individuals and cultured with oxLDL, followed by stimulation with LPS/IFNγ and assessment of the cytokine response. Results: The inflammatory phenotype acquired by macrophages (ex vivo) was related to levels of in vivo circulating lipids. Correlations for CD86/CD163 were found with CVD risk markers; most strongly with triglycerides (TG) and TG/HDL-C, but also with cholesterol/HDL-C and ApoB/ApoA1 and inversely with LDL particle size. Functionally, macrophage production of inflammatory cytokines (TNF and IL-1β) correlated with oxLDL levels and inversely with ApoA1. Macrophages differentiated from monocytes cultured with oxLDL produced significantly higher IL-1β but lower IL-10 (in response to LPS/IFNγ), compared to control cells. Conclusions: Monocyte-derived macrophages adopt an inflammatory phenotype relative to the levels of circulating lipid factors that are characteristic of atherogenic dyslipidaemia (such as high TG, TG/HDL-C and low LDL particle size), but not LDL-C.

Lipidology doi: 10.3390/lipidology2040017

Authors: Julia Emily Steinbeck Rachel Anne Iannotti Adil Rasheed

It has long been recognized that elevated circulating lipid levels are among the strongest risk factors for the development of plaques within the arterial wall that are characteristic of atherosclerotic cardiovascular disease. Indeed, decades of studies have identified the deposition of low-density lipoprotein as an initiator of this disease, which coordinates the vascular and immune dysfunction that fuels the advancement of the atherosclerotic plaque. However, in the vessel wall, deposited cholesterol and fatty acids are dynamic in nature and engage signaling pathways. Shifting from metabolic-related pathways, lipid modifications and their conversion to intermediates engage signaling cascades that further perpetuate the inflammatory milieu of the atherosclerotic plaque and its progression towards the fatal end-stage events associated with cardiovascular disease, including myocardial infarction. In this review, we will cover the cellular and molecular mechanisms that preserve homeostasis and advance disease, including how lipid species induce endothelial dysfunction and drive the development of macrophage foam cells. We will additionally discuss ongoing therapeutic strategies to combat the hyperlipidemia that underlies atherogenesis.

Lipidology doi: 10.3390/lipidology2030016

Authors: Matthias Eckhardt

Lipid droplets are the neutral lipid storage compartments of eukaryotic cells. Mitochondria are the main source for ATP, which is generated through oxidative phosphorylation. Thus, both organelles play essential roles in fatty acid metabolism and energy homeostasis. Therefore, functional and physical interaction of lipid droplets with mitochondria is of special importance as essential processes, such as lipolysis, triacylglycerol synthesis, thermogenesis or the protection against oxidative stress, and lipotoxicity, depend on cooperation of these two organelles. Physical interaction of LDs with mitochondria is mediated by specific molecular complexes at inter-organelle membrane contact sites. Substantial progress has been achieved during the last decade in understanding the formation and the structural components of lipid droplet–mitochondria contact sites. This review gives a brief overview of the different molecular complexes that have been identified in different mammalian cell types under different conditions and their regulation.

Lipidology doi: 10.3390/lipidology2030015

Authors: Tomoko Inoue Keiji Matsunaga Ryosuke Tani Katsufumi Nishioka Sonoko Kondo Takashi Iwase Hai Ying Fu Hayato Tada Masayuki Takamura Takashi Kusaka Tetsuo Minamino

Background: Achilles tendon (AT) thickening reflects cumulative low-density lipoprotein cholesterol (LDL-C) exposure. The Japan Atherosclerosis Society (JAS) explicitly includes AT thickness as a diagnostic criterion for familial hypercholesterolemia (FH) in adults, whereas internationally, it is not a standard diagnostic measure. However, the clinical significance of AT thickening in pediatric populations remains unclear. Methods: We conducted a single-center, retrospective, observational study involving pediatric patients (11–18 years old) with suspected FH through standardized universal lipid screening across Kagawa Prefecture, Japan. Genetic testing confirmed FH through pathogenic variants in the LDLR, PCSK9, or APOB genes. The AT thickness was measured using a standardized ultrasonography protocol. We assessed associations between the FH status, cumulative LDL-C levels, and AT thickness. Results: In the pediatric patients, no significant difference in the AT thickness was observed between the FH and non-FH groups (median 4.4 vs. 4.5 mm; p = 0.570). Cumulative LDL-C was higher in the FH group, while no clear association between cumulative LDL-C and AT thickness was apparent in either group. Conclusions: In this single-center, retrospective study of pediatric patients identified through standardized universal lipid screening, no significant differences were found in AT thickness between FH and non-FH groups although cumulative LDL-C levels were higher in the FH group. Given methodological limitations (small sample size, selection bias, and residual confounding related to statin therapy and growth), these findings should be interpreted as exploratory rather than confirmatory. Regardless of genotype, early risk management may be warranted.

Lipidology doi: 10.3390/lipidology2030014

Authors: Ilenia Milani Ilaria Rossi Giorgia Marodin Maria Giovanna Lupo Maria Pia Adorni Francesca Zimetti Nicola Ferri

Background and aim: ANGPTL3 is a hepatokine acting as a negative regulator of lipoprotein lipase (LPL) through its N-terminal domain. Besides this activity, the C-terminal domain of ANGPTL3 interacts with integrin αVβ3. Since integrins are involved in inflammation and in the initiation of atherosclerotic plaque, the aim of our study was to evaluate the potential direct pro-inflammatory action of ANGPTL3 through the interaction of the fibrinogen-like domain and integrin αVβ3. Methods: We utilized cultured THP-1 human-derived macrophages and evaluated their pro-inflammatory phenotype in response to treatment with human recombinant ANGPTL3 (hANGPTL3). By Western blot, RT-qPCR, biochemical analysis, and ELISA assays, we determined the expression of genes and proteins involved in lipid metabolism and inflammatory response as well as intracellular cholesterol and triglyceride levels. In addition, we evaluated the effect of hANGPTL3 on the cellular cholesterol efflux process. Results: Incubation of THP-1-derived macrophages with 100 ng/mL of hANGPTL3 increased the mRNA expression of the pro-inflammatory cytokines IL-1β, IL-6, and TNFα (respectively, 1.87 ± 0.08-fold, 1.35 ± 0.11-fold, and 2.49 ± 0.43-fold vs. control). The secretion of TNFα, determined by an ELISA assay, was also induced by hANGPTL3 (1.98 ± 0.4-fold vs. control). The pro-inflammatory effect of hANGPTL3 was partially counteracted by co-treatment with the integrin αVβ3 inhibitor RGD peptide, reducing the mRNA levels of IL-1β (3.35 ± 0.35-fold vs. 2.54 ± 0.25-fold for hANGPTL3 vs. hANGPTL3 + RGD, respectively). Moreover, hANGPTL3 reduced cholesterol efflux to apoA-I, with a parallel increase in the intracellular triglyceride and cholesterol contents by 31.2 ± 2.8% and 20.0 ± 4.1%, respectively, compared to the control. Conclusions: ANGPTL3 is an important liver-derived regulator of plasma lipoprotein metabolism, and overall, our results add a new important pro-inflammatory activity of this circulating protein. This new function of ANGPTL3 could also be related to triglyceride and cholesterol accumulation into macrophages.

Lipidology doi: 10.3390/lipidology2030013

Authors: Diana Santos Cabral Andreia Noites

Introduction: Gynoid lipodystrophy (GL) affects most women, manifesting itself from puberty to adulthood. Its multifactorial etiology generates controversy in the literature about the most suitable treatment. Several methods are used, from the smallest to the most invasive, in the search for an effective fight against the severity of GL. The positive effect of ultrasound therapy (US) in decreasing subcutaneous adipose tissue is in increasing the skin permeability of pharmacological molecules, and it has aroused interest in the effect of a combination of the two techniques on the severity of GL. However, the results of this technique associated with an exercise program are unknown. Objective(s): To analyze the effect of three sessions of US + 5% caffeine in association with the realization of an exercise program, in females, on the level of severity of GL in the gluteal region and on the posterior proximal third part of the thigh. Methods: A total of 36 healthy women, aged between 18 and 55, who were considered to have GL, were randomly allocated in two experimental groups and one placebo group. The placebo group (PG) performed only physical exercise during the study. Experimental group 1 (EP1) performed US with 5% caffeine alongside a physical exercise protocol and experimental group 2 (EP2) performed US with a conventional US gel alongside a physical exercise protocol. The three groups completed three intervention sessions over 3 weeks, with one session per week. In addition to the level of severity assessed by the Cellulite Several Scale (CSS), anthropometric measures, body composition, and lipid profile of the participants were evaluated. The first assessment was carried out before the intervention (M0) and the last assessment after the three interventions (M1). The results were analyzed using the ANOVA test. The Tukey test was used for multiple comparisons of the groups in all variables, except for those related to the CSS, where the Kruskal–Wallis test was used with a significance level of 0.05. Results: A total of 29 women completed the study. There was a significant decrease inside the PG related to triglycerides (p = 0.012). In M1, all groups started to present median values below 200 mg of triglycerides. In cholesterol, a significant reduction was observed in all groups (p = 0.05). On the gluteal level at 5 cm, there was a decrease in EP1 and EP2 between M0 and M1 with p = 0.006 and p = 0.002, respectively. On the CSS there were no significant differences between groups or between moments. Conclusions: Three sessions of 5% caffeine and US in association with a physical exercise protocol have no effect on reducing the level of severity of GL.

Lipidology doi: 10.3390/lipidology2020012

Authors: Georgios Kalampounias Panagiotis Katsoris

Microbial lipids are substances of high added value produced by single-cell organisms grown on simple substrates. These lipids, depending on the producing organism, may contain rare fatty acids, whose isolation and purification from non-microbial sources usually is an inefficient and costly procedure. Such fatty acids mostly include members of the omega-3 and omega-6 families of polyunsaturated fatty acids, which are credited with potential anticancer, anti-inflammatory, cardioprotective, and neuroprotective actions. However, their poor solubility in aqueous solutions often restricts their potential applications, as routes other than dietary consumption are unavailable. A promising approach for administering them is their conversion into alkali salts, mostly with lithium or potassium, which are water-soluble and bio-assimilable. In this article, all studies investigating the potential anticancer effects of alkali salts of fatty acids isolated from microorganisms were reviewed in an attempt to sum up existing knowledge and encourage further research.

Lipidology doi: 10.3390/lipidology2020011

Authors: Ellen Aasum Alice M. Pedersen Andreas Hahn Terje S. Larsen Kurt S. Tande

In the first part of this paper, we introduce the marine copepod Calanus finmarchicus, its lifecycle and ecology, and describe the technologies developed for harvesting and extracting oil from this copepod. Calanus oil has a unique composition, with its fatty acids—including a high concentration of long-chain omega-3 polyunsaturated fatty acids (PUFAs) and monounsaturated fatty acids (MUFAs)—bound to long chain fatty alcohols in the form of wax esters. In the second part of this paper, we review pre-clinical and clinical studies conducted over the last two decades, which demonstrate the potential health benefits of Calanus oil. These studies highlight its role in preventing obesity-related metabolic distortions, such as inflammation and reduced insulin sensitivity.

Lipidology doi: 10.3390/lipidology2020010

Authors: Ting Chen Aldo Grefhorst Adriaan G. Holleboom

Background/Objectives: Recent studies show that the gut microbiome plays a pivotal role in the (patho)physiology of metabolic dysfunction-associated steatotic liver disease (MASLD), likely via metabolites they produce that are transported via the portal vein towards the liver where they first encounter liver sinusoidal endothelial cells (LSECs). LSECs may modulate the effects the gut microbes have on the liver, e.g., on the progression of MASLD. Methods: This review aims to describe the current knowledge on the role of LSECs in mediating the effect of gut microbial products in MASLD. Results: Various studies show that LSECS have a contributing role in MASLD pathogenesis, suggesting that proper LSEC functionality is required to protect the liver from gut-driven attacks. Conclusions: Dedicated studies on the role and effects of gut-derived molecules on LSEC functionality are lacking, likely because such studies depend on labor-intensive techniques such as scanning electron microscopy (SEM).

Lipidology doi: 10.3390/lipidology2020009

Authors: Vitor Emanuel de Souza Gomes Paula Fernanda Janetti Bócoli Julia Guirardello Iamarino Renato Grimaldi Ana Paula Badan Ribeiro Luís Marangoni Júnior

Background: Neem seed oil (Azadirachta indica A. Juss) is widely used in the pharmaceutical, agricultural, and food industries due to its antiseptic, fungicidal, pesticidal, and antioxidant properties, attributed to over 300 bioactive compounds and a high content of unsaturated fatty acids. Methods: This study aimed to characterize a commercial sample of neem oil regarding its physicochemical properties and identity profile, using official methodologies from the American Oil Chemists’ Society (AOCS), and to compare the results with literature data. Results: The sample exhibited the following parameters: free fatty acids (2.0 ± 0.02%), acidity index (3.9 ± 0.04 mg KOH/g), peroxide value (3.2 ± 0.1 mEq/kg), iodine value (116 ± 12 g I2/100 g), and saponification index (198 ± 8 mg KOH/g). The predominant coloration was yellowish, with total chlorophyll and carotenoid levels below the equipment’s quantification limits. Fatty acid composition was mainly long-chain (C16–C18), with notable levels of linoleic acid (46%), oleic acid (28%), palmitic acid (12%), linolenic acid (5.5%), and stearic acid (4.1%). The triacylglycerol profile showed a predominance of triunsaturated (51%) and diunsaturated species (41%). Differential scanning calorimetry (DSC) analysis revealed crystallization events between −6 °C and −57 °C and fusion events between −44 °C and −1 °C, consistent with the high unsaturation level of the lipids. Conclusions: The analyzed neem oil sample meets quality and identity criteria, making it suitable for various industrial applications. The characterization confirms its potential and aligns with literature data, emphasizing its relevance for industrial use.

Lipidology doi: 10.3390/lipidology2020008

Authors: Aliute N. S. Udoka Susan K. Duckett

Background: Adipose tissue growth follows a biphasic process involving both cellular hyperplasia (an increase in adipocyte number) and hypertrophy (an increase in adipocyte size). Rumen-protected fatty acid supplements have been utilized to alter fat deposition, modify the fatty acid composition of meat, and reduce methane emissions. However, limited research has explored how different fatty acid mixtures influence adipose tissue’s biphasic growth phases. Methods: The objectives of this study are to investigate the effects of fatty acid mixtures (seven different mixtures) on: (1) hyperplasia of undifferentiated stromal vascular fraction (SVF) cells, or (2) hypertrophy of chemically differentiated SVF cells isolated from subcutaneous adipocytes of finished steers. Results: Mixtures containing palmitic and linoleic acids stimulated hyperplasia, enhancing the proliferation of undifferentiated SVF cells, while mixtures with oleic acid (50%) predominantly promoted hypertrophy, driving lipid accumulation and adipocyte maturation. Conversely, mixtures composed solely of saturated fatty acids (50% palmitic and 50% stearic acids) exhibited a profound inhibitory effect on both hyperplasia and hypertrophy, underscoring the importance of fatty acid composition in regulating adipogenesis. Conclusions: These findings demonstrate that the composition of fatty acid mixtures directly influences adipogenesis and lipogenesis in vitro, highlighting their potential role in designing tailored rumen-protected supplements for modifying fat deposition in livestock.

Lipidology doi: 10.3390/lipidology2020007

Authors: Ezzuddin Abuhussein Luke J. Tucker Andie R. Tubbs Lauren B. Priddy Jessica Amber Jennings

(1) Background: Musculoskeletal trauma from combat wounds, accidents, or surgeries is highly associated with infections and hospitalization. The current “gold standard” for such injuries when access to hospitals is limited is administering antibiotics and opioids; however, they are not ideal treatments due to their contributions to antibiotic resistance and the opioid epidemic. Electrospun chitosan acylated with lipids and loaded with hydrophobic drugs has been shown to release the therapeutics systemically and to prevent infections. (2) Methods: Electrospun chitosan membranes (ESCMs) were fabricated and acylated using decanoyl chloride. FTIR was used to confirm acylation through the presence of ester bonds and acyl chains. ESCMs were loaded with the quorum-sensing molecule cis-2-decenoic acid (C2DA) and the local anesthetic bupivacaine and then implanted in rat femurs for 3 days. Afterward, the rats were euthanized, and CFUs were measured on retrieved bone, tissue, and treatment material. (3) Conclusions: While ESCMs prevented bacterial growth on the surface of the material, controls outperformed treatment groups. This is possibly due to bupivacaine’s role in inhibiting sodium channels, which favors the production of Th2-type cytokines associated with immune response suppression. Furthermore, ESCMs provide a large surface area for bacteria to grow on and form bridges between nanofibers.

Lipidology doi: 10.3390/lipidology2010006

Authors: Feng Ding Wanda J. Weber Rui Su Brian A. Crooker Chi Chen

Background: Genetic selection and improved nutrition and management practices have transformed the Holstein cow. Objectives: This study examined the impacts of 50 years of selection on milk composition during early lactation by comparing milk from contemporary Holsteins (CH) and a unique population of unselected Holsteins (UH) that produce less than half as much milk as their CH herdmates. Methods: Multiparous UH and CH cows (n = 12/genotype) were housed in the same facility, fed the same diets and subjected to the same management procedures. Milk samples were collected weekly through to week 9 of lactation. The proximate composition of milk was determined by infrared spectroscopy and its lipidome by liquid chromatography–mass spectrometry and structural analysis. Data were analyzed as repeated measures using mixed-model procedures with the week of lactation as the repeated effect. Results: An energy balance nadir occurred at week 1 for UH and CH cows but was more severe (−4.5 vs. −14.8 Mcal net energy per day, respectively) for the CH cows. Lipidomic comparison of the 50 most abundant triacylglycerols (TAGs) revealed that CH milk had more TAGs with at least two preformed fatty acids and fewer TAGs with at least two de novo synthesized fatty acids than UH milk. Fatty acid analysis revealed that the increase in preformed fatty acids in CH cows was responsible for the different TAG profiles in UH and CH milk. Furthermore, CH milk contained less free carnitine, short-chain acylcarnitines and lactic acid but more butyric and 3-hydroxybutyric acid than UH milk in early lactation. Conclusions: These results demonstrate that differences in energy balance were primarily responsible for the differences in milk composition between the UH and CH genotypes in early lactation.

Lipidology doi: 10.3390/lipidology2010005

Authors: Vincenzo Alessandro Laudicella Stefano Carboni Cinzia De Vittor Phillip D. Whitfield Mary K. Doherty Adam D. Hughes

Background/Objectives: Gonad histological analysis (GHA) is the traditional method for assessing the gonad maturation status of blue mussels (Mytilus edulis). GHA has some operational disadvantages, such as limited processing outputs, subjectivity in the assessment of transitional stages of gonadal maturation and the need for experienced and trained operators. Lipids could become important indicators of gonadal maturation as they cover many essential functions during such processes in mussels. In this work, blue mussel ovary (BMO) ultrastructure is integrated with liquid chromatography coupled with mass spectrometry (LC-MS) lipidomics fingerprinting to identify suitable markers for ovarian maturation through the application of chemometrics and machine learning approaches. Methods: BMOs are classified here as ripe or non-ripe by means of GHA and the gamete volume fraction (GVF). Receiving operating characteristic (ROC) curves were used to classify the results of the different statistics according to their area under the curve (AUC), and the functional role of important lipids was assessed by lipid ontology enrichment (LiOn) analysis. Results: This approach allowed for the selection of a panel of 35 lipid molecules (AUC > 0.8) that can distinguish non-ripe from ripe BMOs. Ceramide phosphoethanolamine (CerPE) 40:2 was the molecule with the highest classification ability (AUC 0.905), whereas glycerophosphoserine (PS) was the class mostly changing between the two groups. LiOn analysis indicated significant differences in the functional roles of these lipids, highlighting enrichment terms associated with membrane lipids, lysosomes and highly unsaturated triglycerides (TGs) in non-ripe ovaries, whereas terms associated with storage lipids and low-saturated TG characterised ripe BMOs.

Lipidology doi: 10.3390/lipidology2010004

Authors: Caroline Bachmeier Jacobus Ungerer Carel Pretorius Andrew Kassianos Karam M. Kostner

Heterozygous familial hypercholesterolaemia is one of the most common genetic conditions leading to premature atherosclerotic cardiovascular disease. It can be diagnosed using a combination of clinical, biochemical, and genetic tools. Most guidelines recommend screening during childhood and treatment from the age of 8–10 years. However, screening remains sporadic in most countries and the majority of individuals remain undiagnosed. Registry studies have highlighted the ongoing delayed and low percentage of detection of FH in children. Universal early childhood screening models utilising a combination of biomarker-based and genetic testing have been trialled and are in practice in some countries. Newborn screening is a public health success story and one of the most effective public health measures. It offers universal screening for conditions that can result in significant morbidity or even death if left untreated. There has been renewed interest in including familial hypercholesterolaemia in newborn screening programmes. Using cord blood to identify familial hypercholesterolaemia has not yielded convincing results. However, novel screening approaches on dried blood spots that include biomarker-based lipid profile testing alone, in combination with confirmatory genetic testing, or first-line genetic testing have shown promising results. This provides the opportunity of early diagnosis and treatment of infants and their extended families. However, challenges are associated with the inclusion of familial hypercholesterolaemia in newborn screening programmes with significant impacts on the newborn, family members, and public health.

Lipidology doi: 10.3390/lipidology2010003

Authors: Talya Binienda Anna DeMartini Whitney Bullock

In this review paper, we will evaluate LRP4, a low-density lipoprotein receptor-related protein, and its many roles involving myasthenia gravis (MG), Wnt signaling, bone formation and craniofacial development. In MG, LRP4 is critical to the formation of the neuromuscular junction (NMJ) and the key function is to allow for controlled muscle contraction. LRP4 works in combination with agrin and MuSK to form the functional complex. In Wnt signaling, LRP4 was recently identified as a critical player in the pathway for both bone and tooth development and function. Its ability to act as an inhibitor sheds new light on bone formation and resorption. LRP4 binds sclerostin to LRP5 and LRP6, facilitating inhibitory effects important for bone homeostasis and remodeling. In this review paper, we will summarize the known roles of LRP4 as well as explore future directions for research surrounding LRP4 functionality.

Lipidology doi: 10.3390/lipidology2010002

Authors: Angelia M. Holland-Winkler Jonathan J. Ruiz Ramie Andrew R. Moore Austin A. Kohler

Background/Objectives: Firefighters have an elevated risk of developing cardiovascular disease (CVD). Thus, it is vital to determine areas of health associated with the development of CVD that need improvement in the firefighter population, such as circulating lipids and arterial stiffness. The purpose of this study was to assess the potential relationship of lipid and lipoprotein metrics with measures of arterial stiffness in full-time firefighters in the southeastern United States. Methods: Twenty male full-time firefighters underwent a fasted blood draw to assess circulating lipids. Resting arterial stiffness was then assessed via pulse wave velocity (PWV) using an aortic measure. To determine the linear relationships between arterial stiffness and lipid measures of interest, a series of bivariate correlations were conducted as appropriate. The outcome variable was PWV measured continuously in m/s. The predictor variables were total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), small dense LDL-C (sdLDL-C), and triglycerides (TG) measured in mg/dL. All analyses were carried out using SPSS version 29 (α = 0.05). Results: TG levels were positively and moderately correlated with PWV (rs = 0.497, p = 0.026). No other significant relationships were detected between PWV and the remaining variables TC (rs = 0.104, p = 0.664), HDL-C (rs = −0.328, p = 0.158), LDL-C (rs = 0.184, p = 0.436), or sdLDL-C (rs = 0.330, p = 0.155). Conclusion: Higher TG levels are associated with higher PWV and thus, arterial stiffness. Management of circulating TG may be an important consideration in maximizing arterial health and minimizing CVD risk.

Lipidology doi: 10.3390/lipidology2010001

Authors: Roman Voskoboynikov Justin R. DiAngelo

Background/Objectives: Metabolic diseases in humans, such as obesity or type 2 diabetes, arise from defects in the body’s ability to take in and store nutrients such as carbohydrates and triglycerides. Previous studies in the fruit fly, Drosophila melanogaster, have identified SR proteins, mRNA splicing factors that regulate splice-site selection, as regulating lipid storage in the fly fat body. However, whether SR proteins function in other tissues to regulate nutrient metabolism is not known. Methods: We focused on studying the role of SR proteins in intestines by decreasing their levels in the fly gut and measuring the concentrations of lipids and glycogen. Results: We further characterized the intestinal functions of 9G8, an SR protein, which displayed an increase in organismal lipid levels when knocked down in the intestine but had less triglyceride storage in isolated intestines. Interestingly, decreasing 9G8 in the intestine resulted in increased intestinal expression of five fatty acid synthesis/elongation enzyme genes, as well as four triglyceride lipase genes, which may contribute to the triglyceride phenotypes we observed in 9G8-RNAi flies. Conclusions: These data suggest that 9G8 regulates whole body and intestinal lipid homeostasis by altering the expression of lipid metabolic enzyme genes in the fly intestine.

Lipidology doi: 10.3390/lipidology1020010

Authors: Jihoo Woo Russell W. Wiggins Shizue Mito

Niclosamide, an FDA-approved anti-parasitic drug, has demonstrated significant potential as a repurposed anti-cancer agent due to its ability to interfere with multiple oncogenic pathways. However, its clinical application has been hindered by poor solubility and bioavailability. Lipid-based nanocarrier systems such as liposomes, solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), and lipid nanoemulsions (LNE), along with lipid prodrugs, have successfully been employed by researchers to overcome these limitations and improve niclosamide’s pharmacokinetic profile. Lipids are the core organic compounds which serve as the foundation of these advanced drug delivery methods and in turn play a critical role in enhancing niclosamide’s therapeutic efficacy through improving drug solubility and bioavailability. Lipid-based nanoparticles encapsulate niclosamide, protect it from degradation, facilitate drug delivery and release, and may facilitate targeted delivery in the future. While niclosamide holds significant potential as an anticancer agent due to its multi-pathway inhibitory effects, the challenges associated with its poor bioavailability and rapid clearance underscore the need for innovative delivery methods and chemical modifications to unlock its full therapeutic potential. This review aims to present the latest instances of lipid-based delivery of niclosamide and to compile successful strategies which may be employed when aiming to develop effective anticancer therapies.

Lipidology doi: 10.3390/lipidology1020009

Authors: Taylor H. Jacobs Colton D. Wayne Nitin Sajankila Siddharth Narayanan

Dyslipidemia (DL), defined by dysregulated levels of lipids in the bloodstream, is an ever-growing problem in modern society. In addition to those with congenital defects in lipid metabolism, the pervasive nature of high-fat and high-calorie diets in modern industrialized societies has led to a meteoric increase in its incidence. Patients who suffer from this condition subsequently are at a higher risk of developing other co-morbid conditions, most notably diabetes mellitus and coronary artery disease. This review explores another arguably lesser-known consequence of DL, pancreatitis, which is an inflammatory disease of the pancreas. The goal of this article is to review the intersection of these two conditions by briefly highlighting the proposed pathophysiology and exploring the impact of DL (specifically hypertriglyceridemia) on acute, acute recurrent, and chronic pancreatitis. This paper additionally examines the long-term risks of developing pancreatic cancer in patients with pancreatitis secondary to DL and presents unique clinical scenarios that result in DL-associated pancreatitis. Finally, we discuss potential treatment options for hypertriglyceridemia which can potentially mitigate the risk of DL-associated pancreatitis.

Lipidology doi: 10.3390/lipidology1020008

Authors: Marina Nicolaou Meropi Toumba

Background: Lipids encompass a diverse group of biomolecules that are crucial for maintaining the body’s internal equilibrium and for a range of functions, including energy storage, maintenance of cellular membranes, and cellular signalling. Their synthesis and metabolism are intricately linked to hormonal regulation, particularly by thyroid hormones, which influence lipid metabolism by modulating gene expression, enzyme activity, and mitochondrial function. Thyroid hormones enhance the metabolic rate, lipid clearance, and cholesterol conversion to bile acids, which are regulated through feedback mechanisms involving the hypothalamic–pituitary–thyroid axis. Subclinical hypothyroidism (SCH) presents a complex challenge in understanding lipid metabolism. Methods: Research on SCH’s impact on lipid profiles has yielded conflicting results. Some studies indicate that SCH is associated with increased levels of cholesterol and triglycerides, while others report no significant changes. These discrepancies underline the necessity for more comprehensive studies to clarify how SCH affects lipid metabolism and its potential cardiovascular implications. Conclusions: This review aims to consolidate the existing knowledge, exploring the biochemical pathways and clinical evidence that link thyroid dysfunction with lipid abnormalities and cardiovascular health risks. It emphasizes the critical need for further research to elucidate the full impact of SCH on lipid metabolism and its broader effects on cardiovascular health, guiding future interventions and treatment strategies.

Lipidology doi: 10.3390/lipidology1020007

Authors: Michelle C. H. Ng Van Hoan Tran Rujee Kyokajee Duke Catherine A. Offord Patricia F. Meagher Pei Hong Cui Colin Charles Duke

Wollemi pine, Wollemia nobilis W. G. Jones, K. D. Hill & J. M. Allan (Araucariaceae) was discovered in a remote canyon 150 km north-west of Sydney, Australia. As fewer than 100 adult trees of this plant survive in the wild, efforts to conserve this species have included seed storage. Fresh and stored seeds were analysed for yield and composition of the seed oil. The seed kernels, from both fresh and stored seed, were rich in oil with contents of 42% and 48%, respectively. The fatty acid profile of Wollemi pine seed oil was determined by GC-MS analyses of fatty acid methyl ester derivatives. Oleic acid makes up 32% of the fatty acid profile, while the major polyunsaturated fatty acid is linoleic acid (25%). Most of the detectable omega-3 fatty acid content of the oil is α-linolenic acid (3%). The seed oil has a high content of C20 to C24 fatty acids (25%) consisting of long-chain saturated fatty acids (19%). The polyunsaturated C20 omega-6 fatty acid content consists of eicosadienoic acid, dihomo-γ-linolenic acid, and arachidonic acid (total 4%). 1H NMR analyses of the intact oil showed that the lipids were largely in the form of triglycerides with a degree of unsaturation of 1.5 double bond equivalents per fatty acid residue. In artificially aged or stored seeds, minor additional 1H NMR spectral signals were attributed to an omega-3 epoxylipid, tentatively identified as cis-15,16-epoxy-9Z,12Z-octadecadienoic acid or ester derivative. Other minor signals were characteristic of a hydroxy or a hydroperoxy E,Z diene containing fatty acid. These products are typically formed by metabolic lipid oxidation of fatty acids. The content of the omega-3 epoxylipid, determined by the 1H NMR method, varied with storage conditions and duration from less than 0.1% to a maximum of 3.3%.

Lipidology doi: 10.3390/lipidology1010006

Authors: Vassilis Athanasiadis Theodoros Chatzimitakos Dimitrios Kalompatsios Eleni Bozinou Stavros I. Lalas

Blending is a commonly utilized technique for enhancing the oxidative stability, nutritional quality, and physicochemical properties of vegetable oils. This study explored the potential of a vegetable oil blend consisting of common seed oils (sunflower, soybean, rapeseed, cottonseed, and corn oils), through partial least squares analysis, as a substitute for palm oil in the food preparation sector. Oxidative stability assays were conducted initially and after 14 and 28 days of incubation at 60 °C. These assays included radical inhibition activities between the optimal blended oil and palm oil through DPPH• inhibition activity and thermal stability via accelerated oxidation conditions with Rancimat (110 °C, 15 L/h) and conjugated diene and triene formation. The impact of each oil was assessed through correlation analyses and Pareto plots. The optimal blended oil consisted of soybean/sunflower/cottonseed/corn oils at a ratio of 2:1:4:4. It had an induction period (i.e., full rancidity) vastly enhanced to 5.38 h but was statistically significantly lower than the stable palm oil by ~50%. Prior to thermal incubation, the blended oil was more potent in inhibiting DPPH•, as it recorded 139.83 μmol of Trolox equivalents per kg of oil, ~53% more than palm oil. The conjugated diene and triene concentrations were similar for both oils at ~15 and ~7 mmol/kg oil, respectively. The Fourier-Transform Infrared spectra revealed the prevalence of cis fatty acids in the optimal oil blend and trans fatty acids in palm oil, indicating an enhancement in the nutritional quality of the vegetable oil blend. The results of the study could provide a nutritional oil blend that could be used as a substitute for palm oil in the food industry.

Lipidology doi: 10.3390/lipidology1010005

Authors: Senol Dogan Jenny Leopold Daniel T. Hoffmann Hans Kubitschke Eliane Blauth Carlotta Ficorella Amelie Zschau Jürgen Schiller Josef A. Käs

Lipid droplets (LDs) are known to be involved in the invasion and migration of breast cancer (BC) cells. This study aimed to identify LD-associated genes as prognostic markers in BC through comprehensive literature research and integration with lipid composition studies in BC cell lines. The GEPIA platform was used to analyze the differential expression of LD-associated genes in BC. The lipid composition of cell lines (MCF-10A, MDA-MB 436 and 231) was obtained by extraction and thin-layer chromatography coupled with mass spectrometry (MS). Additionally, cell lines were co-cultured with fatty tissue and analyzed by confocal fluorescence microscopy. A total of 143 genes were identified as LD-associated genes through literature research and were subsequently analyzed using GEPIA. Among these, three genes were found to be over-expressed and 45 under-expressed in BC. Notably, FABP7 showed a statistically significant rank for all bioinformatics criteria as a prognostic factor. Experimental results showed only minor changes from MCF-10A to both MDA-MB cell lines for apolar lipids (triacylglycerols and cholesteryl esters) compared to phospholipids (PLs). Microscopic analyses showed that MDA-MB-231 had larger LDs compared to MCF-10A after 10 days of cultivation. Our bioinformatics analysis identified 26 genes that play important roles in metastatic transition in BC via LD-related mechanisms, though these findings could be only partially confirmed by experimental lipid compositional analyses, so far.

Lipidology doi: 10.3390/lipidology1010004

Authors: Gamze Yazar Jozef L. Kokini Brennan Smith

The individual viscoelastic responses of gluten proteins and their lipid-removed counterparts were studied under mixing deformations and small, medium, and large deformations selected in the Large Amplitude Oscillatory Shear (LAOS) sweeps. During Farinograph mixing, gliadin reached the 500 BU consistency line after 3.6 ± 0.4 min, while the highest consistency recorded for lipid-removed gliadin was 268 ± 8.4 BU, suggesting a reduction in the water absorption of gliadin in the absence of lipids. The affinity of glutenin to water increased in the absence of lipids, as development time was reached 11 min earlier for lipid-removed glutenin. Under small LAOS strains, tanδ of gliadin remained constant with the removal of lipids, while glutenin’s elasticity decreased (tanδ increased) in the absence of lipids at high frequencies. Intracycle strain-stiffening behavior (e3/e1 > 0) of gliadin increased under medium deformations with high frequency and decreased under low-frequency large deformations as lipids were removed, while this response decreased for glutenin with the removal of lipids only under high-frequency medium and large deformations. Under large LAOS strains, the clockwise rotation of the Lissajous–Bowditch curves for gliadin in the absence of lipids suggested higher intercycle strain-softening and shear-thinning, while the counter-clockwise rotation of the curves for glutenin in the absence of lipids suggested lower intercycle strain-softening and shear-thinning. These results revealed the influence of endogenous lipids on the viscous-dominated response of gliadin and to the elastic-dominated response of glutenin, while balancing the intracycle strain-stiffening behaviors of these gluten proteins especially under large deformations.

Lipidology doi: 10.3390/lipidology1010003

Authors: Igor S. Flores Daniel L. R. Annunciação Vinícius S. Pinto Luciano M. Lião

Edible oils have commercial and nutritional value due to the presence of essential fatty acids. They can be consumed fresh in the form of capsules known as nutraceuticals. The quality of such products is of interest to the consumer. In this context, this study describes a method based on high-resolution nuclear magnetic resonance (NMR) and Fourier-transform mid-infrared spectroscopic analysis (FTIR), combined with statistical analyses, to differentiate different edible oils used as nutraceuticals in Brazil by fatty acid content. Through the analysis of 1H NMR spectra, the levels of saturated and unsaturated fatty acids in edible oils were characterized and quantified. Statistical analysis of the data confirmed the real distinctions between nutraceutical raw materials, with emphasis on ω-9, ω-6, and ω-3 fatty acids. The analytical approach presented also demonstrates the potential to identify the origin (animal or vegetable) of edible oils used as nutraceuticals.

Lipidology doi: 10.3390/lipidology1010002

Authors: Rob C. A. Keller

The precise role of protein–lipid interactions in protein translocation is, after almost four decades of research, still a matter of debate. The experimental evidence, as described in the literature, indicates that (anionic) phospholipids play a role in numerous events in protein translocation; however, its meaning and relevance are still a matter of debate. This study tries to fill some missing links in the experimental evidence by means of in silico experiments. The study presented here indicates not only that there is a direct signal sequence–phospholipid interaction but also that the corresponding signal peptides can translocate additional amino acids across a pure lipid membrane. Furthermore, results are presented when it comes to the extent of anionic phospholipids’ dependence on this process. The correlations between the in silico results of pure signal peptide–phospholipid interactions and the observed experimental trends in the overall protein translocation effects are at least remarkable. The results emphasize that new models for protein translocation will have to be developed to take all these and previous experimental data into account.

Lipidology doi: 10.3390/lipidology1010001

Authors: Nicola Ferri

On behalf of all the Editorial Board members and MDPI staff, I am pleased to announce the publication of the inaugural issue of the Lipidology journal [...]