Lipidology

(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

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%. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article