Lipidology, Volume 3, Issue 2 (June 2026) – 9 articles

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article