Lipidology

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