Lipidology

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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). Full article

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. Full article

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. Full article

(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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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 (r_s = 0.497, p = 0.026). No other significant relationships were detected between PWV and the remaining variables TC (r_s = 0.104, p = 0.664), HDL-C (r_s = −0.328, p = 0.158), LDL-C (r_s = 0.184, p = 0.436), or sdLDL-C (r_s = 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. Full article

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. Full article

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. Full article

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. Full article

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. Full article