Progress in Lipid Research

Dihydroceramide desaturase 1 (DEGS1) converts dihydroceramide (dhCer) to ceramide (Cer) by inserting a C4-C5 trans (∆4E) double bond into the sphingoid backbone. Low DEGS activity causes accumulation of dihydroceramide and other dihydrosphingolipid species. Although dhCer and Cer are structurally very similar, their imbalances can have major consequences both in vitro and in vivo. Mutations in the human DEGS1 gene are known to cause severe neurological defects, such as hypomyelinating leukodystrophy...

Lipids play important roles in energy metabolism along with diverse aspects of biological membrane structure, signaling and other functions. Perturbations of lipid metabolism are responsible for the development of various pathologies comprising metabolic syndrome, obesity, and type 2 diabetes. Accumulating evidence suggests that circadian oscillators, operative in most cells of our body, coordinate temporal aspects of lipid homeostasis. In this review we summarize current knowledge on the circadian regulation of lipid digestion, absorption, transportation, biosynthesis, catabolism, and storage...

Plasmalogen is a major phospholipid of mammalian cell membranes. Recently it is becoming evident that the sn-1 vinyl-ether linkage in plasmalogen, contrasting to the ester linkage in the counterpart diacyl glycerophospholipid, yields differential molecular characteristics for these lipids especially related to hydrocarbon-chain order, so as to concertedly regulate biological membrane processes. A role played by NMR in gaining information in this respect, ranging from molecular to tissue levels, draws particular attention...

Mammalian lipid droplets (LDs) are specialized cytosolic organelles consisting of a neutral lipid core surrounded by a membrane made up of a phospholipid monolayer and a specific population of proteins that varies according to the location and function of each LD. Over the past decade, there have been significant advances in the understanding of LD biogenesis and functions. LDs are now recognized as dynamic organelles that participate in many aspects of cellular homeostasis plus other vital functions. LD biogenesis is a complex, highly-regulated process with assembly occurring on the endoplasmic reticulum although aspects of the underpinning molecular mechanisms remain elusive...

Branched-chain fatty acids (BCFA) are a group of lipids that are widely present in various organisms; they take part in numerous biochemical processes and affect multiple signaling pathways. However, BCFA are not well explored in terms of their effects on human health. Recently, they have been gaining interest, especially in relation to various human diseases. This review describes the occurrence of BCFA, their dietary sources, their potential health effects, and the current state of knowledge concerning their mechanism(s) of action...

Disturbances of lipid homeostasis in cells provoke human diseases. The elucidation of the underlying mechanisms and the development of efficient therapies represent formidable challenges for biomedical research. Exemplary cases are two rare, autosomal recessive, and ultimately fatal lysosomal diseases historically named "Niemann-Pick" honoring the physicians, whose pioneering observations led to their discovery. Acid sphingomyelinase deficiency (ASMD) and Niemann-Pick type C disease (NPCD) are caused by specific variants of the sphingomyelin phosphodiesterase 1 (SMPD1) and NPC intracellular cholesterol transporter 1 (NPC1) or NPC intracellular cholesterol transporter 2 (NPC2) genes that perturb homeostasis of two key membrane components, sphingomyelin and cholesterol, respectively...

Huntington disease (HD) is a debilitating, currently incurable disease. Protein aggregation and metabolic deficits are pathological hallmarks but their link to neurodegeneration and symptoms remains debated. Here, we summarize alterations in the levels of different sphingolipids in an attempt to characterize sphingolipid patterns specific to HD, an additional molecular hallmark of the disease. Based on the crucial role of sphingolipids in maintaining cellular homeostasis, the dynamic regulation of sphingolipids upon insults and their involvement in cellular stress responses, we hypothesize that maladaptations or blunted adaptations, especially following cellular stress due to reduced oxygen supply (hypoxia) contribute to the development of pathology in HD...

Alzheimer's disease (AD) diagnosis is based on invasive and expensive biomarkers. Regarding AD pathophysiological mechanisms, there is evidence of a link between AD and aberrant lipid homeostasis. Alterations in lipid composition have been observed in blood and brain samples, and transgenic mouse models represent a promising approach. Nevertheless, there is great variability among studies in mice for the determination of different types of lipids in targeted and untargeted methods. It could be explained by the different variables (model, age, sex, analytical technique), and experimental conditions used...

We are presenting new evidence on essential fatty acids (EFA) in prenatal human development. We have demonstrated, for the first time, the detailed process of active selection of some fatty acids by the placenta (biomagnification) and rejection of others (bioreduction) and how this strategy is of supreme importance for understanding of the biology of human reproduction. The biomagnification process by the placenta is dominated by arachidonic acid (ArA) and its allies: di-homo-gamma-linolenic acid (DGLA), adrenic acid and ω6 docosapentaenoic acid...

No abstract text is available yet for this article.

Consumption of diets rich in fruits and vegetables, which provide some fat-soluble vitamins and many phytochemicals, is associated with a lower risk of developing certain degenerative diseases. It is well accepted that not only the parent compounds, but also their derivatives formed upon enzymatic or nonenzymatic transformations, can produce protective biological effects. These derivatives can be formed during food storage, processing, or cooking. They can also be formed in the lumen of the upper digestive tract during digestion, or via metabolism by microbiota in the colon...

It is well established that bile acids play important roles in lipid metabolism. In recent decades, bile acids have also been shown to function as signaling molecules via interacting with various receptors. Bile acids circulate continuously through the enterohepatic circulation and go through microbial transformation by gut microbes, and thus bile acids metabolism has profound effects on the liver and intestinal tissues as well as the gut microbiota. Farnesoid X receptor and G protein-coupled bile acid receptor 1 are two pivotal bile acid receptors that highly expressed in the intestinal tissues, and they have emerged as pivotal regulators in bile acids metabolism, innate immunity and inflammatory responses...

No abstract text is available yet for this article.

Atherosclerotic cardiovascular disease (ASCVD) is one of the major leading global causes of death. Genetic and epidemiological studies strongly support the causal association between triacylglycerol-rich lipoproteins (TAGRL) and atherogenesis, even in statin-treated patients. Recent genetic evidence has clarified that variants in several key genes implicated in TAGRL metabolism are strongly linked to the increased ASCVD risk. There are several triacylglycerol-lowering agents; however, new therapeutic options are in development, among which are miRNA-based therapeutic approaches...

It is now well established that vitamins D, E, and K and carotenoids are not absorbed solely through passive diffusion. Broad-specificity membrane transporters such as SR-BI (scavenger receptor class B type I), CD36 (CD36 molecule), NPC1L1 (Niemann Pick C1-like 1) or ABCA1 (ATP-binding cassette A1) are involved in the uptake of these micronutrients from the lumen to the enterocyte cytosol and in their secretion into the bloodstream. Recently, the existence of efflux pathways from the enterocyte back to the lumen or from the bloodstream to the lumen, involving ABCB1 (P-glycoprotein/MDR1) or the ABCG5/ABCG8 complex, has also been evidenced for vitamins D and K...

Atherosclerotic cardiovascular disease is one of the major leading global causes of death. Growing evidence has demonstrated that gut microbiota (GM) and its metabolites play a pivotal role in the onset and progression of atherosclerosis (AS), now known as GM-artery axis. There are interactions between dietary lipids and GM, which ultimately affect GM and its metabolites. Given these two aspects, the GM-artery axis may play a mediating role between dietary lipids and AS. Diets rich in saturated fatty acids (SFAs), omega-6 polyunsaturated fatty acids (n-6 PUFAs), industrial trans fatty acids (TFAs), and cholesterol can increase the levels of atherogenic microbes and metabolites, whereas monounsaturated fatty acids (MUFAs), ruminant TFAs, and phytosterols (PS) can increase the levels of antiatherogenic microbes and metabolites...

Perturbations in lipid homeostasis combined with conditions favoring oxidative stress constitute a hallmark of the inflammatory response. In this review we focus on the most recent results concerning lipid signaling in various oxidative stress-mediated responses and inflammation. These include phagocytosis and ferroptosis. The best characterized event, common to these responses, is the synthesis of oxygenated metabolites of arachidonic acid and other polyunsaturated fatty acids. Major developments in this area have highlighted the importance of compartmentalization of the enzymes and lipid substrates in shaping the appropriate response...

The trans fatty acids (TFAs) in food are mainly generated from the ruminant animals (meat and milk) and processed oil or oil products. Excessive intake of TFAs (>1% of total energy intake) caused more than 500,000 deaths from coronary heart disease and increased heart disease risk by 21% and mortality by 28% around the world annually, which will be eliminated in industrially-produced trans fat from the global food supply by 2023. Herein, we aim to provide a comprehensive overview of the biological effects, analytical methods, formation and mitigation measures of TFAs in food...

The endoplasmic reticulum (ER) is a complex and dynamic organelle that regulates many cellular pathways, including protein synthesis, protein quality control, and lipid synthesis. When one or multiple ER roles are dysregulated and saturated, the ER enters a stress state, which, in turn, activates the highly conserved unfolded protein response (UPR). By sensing the accumulation of unfolded proteins or lipid bilayer stress (LBS) at the ER, the UPR triggers pathways to restore ER homeostasis and eventually induces apoptosis if the stress remains unresolved...

The role of omega-3 polyunsaturated fatty acids (PUFAs) in primary and secondary prevention on major cardiovascular events (MCE) is inconclusive due to the potential heterogeneity in study designs of formulas, dosages, and ratios of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from the findings of previous randomized controlled trials (RCTs). Here we conducted a comprehensive narrative review of pre-clinical studies and updated a network meta-analysis (NMA) to determine the comparative efficacy against MCE with different EPA/DHA dosages and formulas...