0
selected
-
1.
The lipid raft markers stomatin, prohibitin, flotillin, and HflK/C (SPFH)-domain proteins form an operon with NfeD proteins and function with apolar polyisoprenoid lipids.
Yokoyama, H, Matsui, I
Critical reviews in microbiology. 2020;(1):38-48
Abstract
SPFH-domain proteins are found in almost all organisms across three domains: archaea, bacteria, and eukaryotes. In eukaryotic organelles, their subfamilies exhibit overlapping distribution and functions; thus, the rationality of annotation to discriminate these subfamilies remains unclear. In this review, the binding ability of prokaryotic SPFH-domain proteins towards nonpolar polyisoprenoides such as squalene and lycopene, rather than cholesterol, is discussed. The hydrophobic region at the C-terminus of SPFH-domain proteins constitutes the main region that binds apolar polyisoprenoid lipids as well as cholesterol and substantively contributes towards lipid raft formation as these regions are self-assembled together with specific lipids. Because the scaffolding proteins caveolins show common topological properties with SPFH-domain proteins such as stomatin and flotillin, the α-helical segments of stomatin proteins can flexibly move along with the membrane surface, with such movement potentially leading to membrane bending via lipid raft clustering through the formation of high order homo-oligomeric complexes of SPFH-domain proteins. We also discuss the functional significance and ancient origin of SPFH-domain proteins and the NfeD protein (STOPP) operon, which can be traced back to the ancient living cells that diverged and evolved to archaea and bacteria. Based on the molecular mechanism whereby the STOPP-protease degrades the C-terminal hydrophobic clusters of SPFH-domain proteins, it is conceivable that STOPP-protease might control the physicochemical properties of lipid rafts.
-
2.
The influence of dietary fatty acids on liver fat content and metabolism.
Hodson, L, Rosqvist, F, Parry, SA
The Proceedings of the Nutrition Society. 2020;(1):30-41
Abstract
Non-alcoholic fatty liver disease encompasses a spectrum of conditions from hepatic steatosis through to cirrhosis; obesity is a known risk factor. The liver plays a major role in regulating fatty acid metabolism and perturbations in intrahepatic processes have potential to impact on metabolic health. It remains unclear why intra-hepatocellular fat starts to accumulate, but it likely involves an imbalance between fatty acid delivery to the liver, fatty acid synthesis and oxidation within the liver and TAG export from the liver. As man spends the majority of the day in a postprandial rather than postabsorptive state, dietary fatty acid intake should be taken into consideration when investigating why intra-hepatic fat starts to accumulate. This review will discuss the impact of the quantity and quality of dietary fatty acids on liver fat accumulation and metabolism, along with some of the potential mechanisms involved. Studies investigating the role of dietary fat in liver fat accumulation, although surprisingly limited, have clearly demonstrated that it is total energy intake, rather than fat intake per se, that is a key mediator of liver fat content; hyperenergetic diets increase liver fat whilst hypoenergetic diets decrease liver fat content irrespective of total fat content. Moreover, there is now, albeit limited evidence emerging to suggest the composition of dietary fat may also play a role in liver fat accumulation, with diets enriched in saturated fat appearing to increase liver fat content to a greater extent when compared with diets enriched in unsaturated fats.
-
3.
Obesity, Bioactive Lipids, and Adipose Tissue Inflammation in Insulin Resistance.
Kojta, I, Chacińska, M, Błachnio-Zabielska, A
Nutrients. 2020;(5)
Abstract
Obesity is a major risk factor for the development of insulin resistance and type 2 diabetes. The exact mechanism by which adipose tissue induces insulin resistance is still unclear. It has been demonstrated that obesity is associated with the adipocyte dysfunction, macrophage infiltration, and low-grade inflammation, which probably contributes to the induction of insulin resistance. Adipose tissue synthesizes and secretes numerous bioactive molecules, namely adipokines and cytokines, which affect the metabolism of both lipids and glucose. Disorders in the synthesis of adipokines and cytokines that occur in obesity lead to changes in lipid and carbohydrates metabolism and, as a consequence, may lead to insulin resistance and type 2 diabetes. Obesity is also associated with the accumulation of lipids. A special group of lipids that are able to regulate the activity of intracellular enzymes are biologically active lipids: long-chain acyl-CoAs, ceramides, and diacylglycerols. According to the latest data, the accumulation of these lipids in adipocytes is probably related to the development of insulin resistance. Recent studies indicate that the accumulation of biologically active lipids in adipose tissue may regulate the synthesis/secretion of adipokines and proinflammatory cytokines. Although studies have revealed that inflammation caused by excessive fat accumulation and abnormalities in lipid metabolism can contribute to the development of obesity-related insulin resistance, further research is needed to determine the exact mechanism by which obesity-related insulin resistance is induced.
-
4.
Role of dyslipidemia in accelerating inflammation, autoimmunity, and atherosclerosis in systemic lupus erythematosus and other autoimmune diseases.
Wang, Y, Yu, H, He, J
Discovery medicine. 2020;(159):49-56
Abstract
Dyslipidemia refers to the abnormality of lipid metabolism. The aberrant lipid profiles are usually characterized by elevated plasma levels of low-density lipoprotein cholesterol (LDL-c), total cholesterol (TC), triglycerides (TGs), apoprotein B (ApoB), and decreased level of high-density lipoprotein cholesterol (HDL-c). Dyslipidemia occurs frequently in autoimmune diseases (ADs), such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), type-1 diabetes mellitus (T1DM), psoriasis, and inflammatory bowel disease (IBD), and many other diseases. An imbalance in lipid metabolism contributes to accelerated inflammatory responses in addition to promoting the formation of atherosclerosis. Although there have been many studies and reports on the relationship between abnormal lipid metabolism and ADs, it remains uncertain as to whether dyslipidemia has a unique role in promoting the occurrence and development of ADs. Here, we discuss the mechanisms of how dyslipidemia accelerates inflammatory response, autoimmunity, and atherosclerosis at epidemiological, molecular, and cellular levels, and the discussion is mainly conducted with SLE as an example.
-
5.
Lipid composition of the cancer cell membrane.
Szlasa, W, Zendran, I, Zalesińska, A, Tarek, M, Kulbacka, J
Journal of bioenergetics and biomembranes. 2020;(5):321-342
-
-
Free full text
-
Abstract
Cancer cell possesses numerous adaptations to resist the immune system response and chemotherapy. One of the most significant properties of the neoplastic cells is the altered lipid metabolism, and consequently, the abnormal cell membrane composition. Like in the case of phosphatidylcholine, these changes result in the modulation of certain enzymes and accumulation of energetic material, which could be used for a higher proliferation rate. The changes are so prominent, that some lipids, such as phosphatidylserines, could even be considered as the cancer biomarkers. Additionally, some changes of biophysical properties of cell membranes lead to the higher resistance to chemotherapy, and finally to the disturbances in signalling pathways. Namely, the increased levels of certain lipids, like for instance phosphatidylserine, lead to the attenuation of the immune system response. Also, changes in lipid saturation prevent the cells from demanding conditions of the microenvironment. Particularly interesting is the significance of cell membrane cholesterol content in the modulation of metastasis. This review paper discusses the roles of each lipid type in cancer physiology. The review combined theoretical data with clinical studies to show novel therapeutic options concerning the modulation of cell membranes in oncology.
-
6.
Pleiotropic effects of polyphenols on glucose and lipid metabolism: Focus on clinical trials.
Matacchione, G, Gurău, F, Baldoni, S, Prattichizzo, F, Silvestrini, A, Giuliani, A, Pugnaloni, A, Espinosa, E, Amenta, F, Bonafè, M, et al
Ageing research reviews. 2020;:101074
Abstract
Epidemiological evidence from observational studies suggests that dietary polyphenols (PPs) - phytochemicals found in a variety of plant-based foods - can reduce the risk of developing type 2 diabetes mellitus (T2DM). Clinical trials have also indicated that PPs may help manage the two key features of T2DM, hyperglycemia and dyslipidemia. Since the incidence of T2DM is dramatically increasing worldwide, identifying food-based approaches that can reduce the risk of developing it and help manage its main risk factors in early-stage disease has clinical and socioeconomic relevance. After a brief overview of current epidemiological data on the incidence of T2DM in individuals consuming PP-rich diets, we review the evidence from clinical trials investigating PP-enriched foods and/or PP-based nutraceutical compounds, report their main results, and highlight the knowledge gaps that should be bridged to enhance our understanding of the role of PPs in T2DM development and management.
-
7.
Dysregulated lipid metabolism links NAFLD to cardiovascular disease.
Deprince, A, Haas, JT, Staels, B
Molecular metabolism. 2020;:101092
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is rapidly becoming a global health problem. Cardiovascular diseases (CVD) are the most common cause of mortality in NAFLD patients. NAFLD and CVD share several common risk factors including obesity, insulin resistance, and type 2 diabetes (T2D). Atherogenic dyslipidemia, characterized by plasma hypertriglyceridemia, increased small dense low-density lipoprotein (LDL) particles, and decreased high-density lipoprotein cholesterol (HDL-C) levels, is often observed in NAFLD patients. SCOPE OF REVIEW In this review, we highlight recent epidemiological studies evaluating the link between NAFLD and CVD risk. We further focus on recent mechanistic insights into the links between NAFLD and altered lipoprotein metabolism. We also discuss current therapeutic strategies for NAFLD and their potential impact on NAFLD-associated CVD risk. MAJOR CONCLUSIONS Alterations in hepatic lipid and lipoprotein metabolism are major contributing factors to the increased CVD risk in NAFLD patients, and many promising NASH therapies in development also improve dyslipidemia in clinical trials.
-
8.
The role of β-carotene and vitamin A in atherogenesis: Evidences from preclinical and clinical studies.
Miller, AP, Coronel, J, Amengual, J
Biochimica et biophysica acta. Molecular and cell biology of lipids. 2020;(11):158635
-
-
Free full text
-
Abstract
Atherosclerotic cardiovascular disease (ASCVD) is the principal contributor to myocardial infarction, the leading cause of death worldwide. Epidemiological and mechanistic studies indicate that β-carotene and its vitamin A derivatives stimulate lipid catabolism in several tissues to reduce the incidence of obesity, but their roles within ASCVD are elusive. Herein, we review the mechanisms by which β-carotene and vitamin A modulate ASCVD. First, we summarize the current knowledge linking these nutrients with epidemiological studies and lipoprotein metabolism as one of the initiating factors of ASCVD. Next, we focus on different aspects of vitamin A metabolism in immune cells such as the mechanisms of carotenoid uptake and conversion to the vitamin A metabolite, retinoic acid. Lastly, we review the effects of retinoic acid on immuno-metabolism, differentiation, and function of macrophages and T cells, the two pillars of the innate and adaptive immune response in ASCVD, respectively. This article is part of a Special Issue entitled Carotenoids recent advances in cell and molecular biology edited by Johannes von Lintig and Loredana Quadro.
-
9.
Rewiring of Lipid Metabolism in Adipose Tissue Macrophages in Obesity: Impact on Insulin Resistance and Type 2 Diabetes.
Dahik, VD, Frisdal, E, Le Goff, W
International journal of molecular sciences. 2020;(15)
Abstract
Obesity and its two major comorbidities, insulin resistance and type 2 diabetes, represent worldwide health issues whose incidence is predicted to steadily rise in the coming years. Obesity is characterized by an accumulation of fat in metabolic tissues resulting in chronic inflammation. It is now largely accepted that adipose tissue inflammation underlies the etiology of these disorders. Adipose tissue macrophages (ATMs) represent the most enriched immune fraction in hypertrophic, chronically inflamed adipose tissue, and these cells play a key role in diet-induced type 2 diabetes and insulin resistance. ATMs are triggered by the continuous influx of dietary lipids, among other stimuli; however, how these lipids metabolically activate ATM depends on their nature, composition and localization. This review will discuss the fate and molecular programs elicited within obese ATMs by both exogenous and endogenous lipids, as they mediate the inflammatory response and promote or hamper the development of obesity-associated insulin resistance and type 2 diabetes.
-
10.
Inhibitors of lipogenic enzymes as a potential therapy against cancer.
Montesdeoca, N, López, M, Ariza, X, Herrero, L, Makowski, K
FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2020;(9):11355-11381
Abstract
Cancer cells rely on several metabolic pathways such as lipid metabolism to meet the increase in energy demand, cell division, and growth and successfully adapt to challenging environments. Fatty acid synthesis is therefore commonly enhanced in many cancer cell lines. Thus, relevant efforts are being made by the scientific community to inhibit the enzymes involved in lipid metabolism to disrupt cancer cell proliferation. We review the rapidly expanding body of inhibitors that target lipid metabolism, their side effects, and current status in clinical trials as potential therapeutic approaches against cancer. We focus on their molecular, biochemical and structural properties, selectivity and effectiveness and discuss their potential role as antitumor drugs.