scispace - formally typeset
Search or ask a question
Journal ArticleDOI

The critical role of phosphatidylcholine and phosphatidylethanolamine metabolism in health and disease.

01 Sep 2017-Biochimica et Biophysica Acta (Biochim Biophys Acta Biomembr)-Vol. 1859, Iss: 9, pp 1558-1572
TL;DR: Data showing that changes in the PC and/or PE content of various tissues are implicated in metabolic disorders such as atherosclerosis, insulin resistance and obesity is highlighted.
About: This article is published in Biochimica et Biophysica Acta.The article was published on 2017-09-01 and is currently open access. It has received 719 citations till now. The article focuses on the topics: Lipid droplet & Phospholipid.
Citations
More filters
Journal ArticleDOI
TL;DR: A comprehensive understanding of the metabolic adaptations involved in insulin resistance may enable the identification of novel targets for improving insulin sensitivity and preventing, and treating, T2DM.
Abstract: The cause of insulin resistance in obesity and type 2 diabetes mellitus (T2DM) is not limited to impaired insulin signalling but also involves the complex interplay of multiple metabolic pathways. The analysis of large data sets generated by metabolomics and lipidomics has shed new light on the roles of metabolites such as lipids, amino acids and bile acids in modulating insulin sensitivity. Metabolites can regulate insulin sensitivity directly by modulating components of the insulin signalling pathway, such as insulin receptor substrates (IRSs) and AKT, and indirectly by altering the flux of substrates through multiple metabolic pathways, including lipogenesis, lipid oxidation, protein synthesis and degradation and hepatic gluconeogenesis. Moreover, the post-translational modification of proteins by metabolites and lipids, including acetylation and palmitoylation, can alter protein function. Furthermore, the role of the microbiota in regulating substrate metabolism and insulin sensitivity is unfolding. In this Review, we discuss the emerging roles of metabolites in the pathogenesis of insulin resistance and T2DM. A comprehensive understanding of the metabolic adaptations involved in insulin resistance may enable the identification of novel targets for improving insulin sensitivity and preventing, and treating, T2DM.

293 citations

Journal ArticleDOI
TL;DR: Mounting evidence suggests that changes in LPCAT activity may be potentially involved in pathological conditions, including nonalcoholic fatty liver disease, atherosclerosis, viral infections, and cancer, and Pharmacological manipulation of L PCAT activity and membrane phospholipid composition may provide new therapeutic options for these conditions.
Abstract: Phospholipids are major constituents of biological membranes. The fatty acyl chain composition of phospholipids determines the biophysical properties of membranes and thereby affects their impact on biological processes. The composition of fatty acyl chains is also actively regulated through a deacylation and reacylation pathway called Lands' cycle. Recent studies of mouse genetic models have demonstrated that lysophosphatidylcholine acyltransferases (LPCATs), which catalyze the incorporation of fatty acyl chains into the sn-2 site of phosphatidylcholine, play important roles in pathophysiology. Two LPCAT family members, LPCAT1 and LPCAT3, have been particularly well studied. LPCAT1 is crucial for proper lung function due to its role in pulmonary surfactant biosynthesis. LPCAT3 maintains systemic lipid homeostasis by regulating lipid absorption in intestine, lipoprotein secretion, and de novo lipogenesis in liver. Mounting evidence also suggests that changes in LPCAT activity may be potentially involved in pathological conditions, including nonalcoholic fatty liver disease, atherosclerosis, viral infections, and cancer. Pharmacological manipulation of LPCAT activity and membrane phospholipid composition may provide new therapeutic options for these conditions.

205 citations

Journal ArticleDOI
TL;DR: In this article, the impact of composition on liposome synthesis, function, and clinical utility is discussed, as well as the role of composition of liposomes in drug delivery.

179 citations

Journal ArticleDOI
TL;DR: Some key regulatory mechanisms that control ER‐localized enzyme activities in animal cells are highlighted and how they act in concert to maintain cellular lipid homeostasis is discussed, as well as how their dysregulation contributes to human disease.
Abstract: Endoplasmic reticulum (ER)‐localized enzymes synthesize the vast majority of cellular lipids. The ER therefore has a major influence on cellular lipid biomass and balances the production of different lipid categories, classes, and species. Signals from outside and inside the cell are directed to ER‐localized enzymes, and lipid enzyme activities are defined by the integration of internal, homeostatic, and external information. This allows ER‐localized lipid synthesis to provide the cell with membrane lipids for growth, proliferation, and differentiation‐based changes in morphology and structure, and to maintain membrane homeostasis across the cell. ER enzymes also respond to physiological signals to drive carbohydrates and nutritionally derived lipids into energy‐storing triglycerides. In this review, we highlight some key regulatory mechanisms that control ER‐localized enzyme activities in animal cells. We also discuss how they act in concert to maintain cellular lipid homeostasis, as well as how their dysregulation contributes to human disease.

151 citations


Cites background from "The critical role of phosphatidylch..."

  • ...This genetic manipulation not only corrected the PtdCho/PtdEtn imbalance, but also reduced ER dysfunction in the mice including restoring the function of the SERCA calcium pump that has a well-characterized sensitivity to ER membrane composition [125] (Fig 3C)....

    [...]

01 Jan 2003
TL;DR: It is concluded that apoB100-lipoproteins exit the ER in COPII vesicles, but under conditions favorable for VLDL formation final lipid loading occurs post-ER.
Abstract: SUMMARY Hepatic apolipoprotein B100 (apoB100) associates with lipids to form dense lipoprotein particles in the ER and is further lipidated to very low density lipoproteins (VLDL). Because the VLDL diameter can exceed 200 nm, classical ER-derived vesicles may be unable to accommodate VLDLs. Using hepatic membranes and cytosol to reconstitute ER budding, apoB100-containing vesicles sedimented distinct from those harboring more typical cargo but contained Sec23. Moreover, ER exit of apoB was inhibited by dominant-negative Sar1. Budding required Sar1 regardless of whether oleic acid (OA) was added to stimulate apoB lipidation; therefore, either large apoB100-lipoproteins reside in secretory vesicles or full lipidation occurs post-ER. Using membranes from cells incubated in the presence or absence of OA, we determined that apoB100-lipoproteins in ER-vesicles had not become lipidated to VLDLs. VLDL particles resided in the Golgi, but not the ER, after fractionation of OA-treated cells. We conclude that apoB100-lipoproteins exit the ER in COPII vesicles, but under conditions favorable for VLDL formation final lipid loading occurs post-ER. 2

134 citations

References
More filters
Journal ArticleDOI
TL;DR: The complex, interdigitated roles of these three SREBPs have been dissected through the study of ten different lines of gene-manipulated mice and form the subject of this review.
Abstract: Lipid homeostasis in vertebrate cells is regulated by a family of membrane-bound transcription factors designated sterol regulatory element–binding proteins (SREBPs). SREBPs directly activate the expression of more than 30 genes dedicated to the synthesis and uptake of cholesterol, fatty acids, triglycerides, and phospholipids, as well as the NADPH cofactor required to synthesize these molecules (1–4). In the liver, three SREBPs regulate the production of lipids for export into the plasma as lipoproteins and into the bile as micelles. The complex, interdigitated roles of these three SREBPs have been dissected through the study of ten different lines of gene-manipulated mice. These studies form the subject of this review.

4,406 citations

Journal ArticleDOI
02 May 1997-Cell
TL;DR: This research was supported by grants from the National Institutes of Health (HL20948) and the Perot Family Foundation.

3,626 citations

Journal ArticleDOI
TL;DR: Recent advances have uncovered mechanisms by which the intestinal mucosal barrier is regulated in response to physiological and immunological stimuli, along with evidence that this regulation shapes mucosal immune responses in the gut and, when dysfunctional, may contribute to disease.
Abstract: Mucosal surfaces are lined by epithelial cells. These cells establish a barrier between sometimes hostile external environments and the internal milieu. However, mucosae are also responsible for nutrient absorption and waste secretion, which require a selectively permeable barrier. These functions place the mucosal epithelium at the centre of interactions between the mucosal immune system and luminal contents, including dietary antigens and microbial products. Recent advances have uncovered mechanisms by which the intestinal mucosal barrier is regulated in response to physiological and immunological stimuli. Here I discuss these discoveries along with evidence that this regulation shapes mucosal immune responses in the gut and, when dysfunctional, may contribute to disease.

2,795 citations

Journal ArticleDOI
TL;DR: Recent advances in the understanding of the molecular events contributing to hepatic steatosis and nonalcoholic steatohepatitis are highlighted.
Abstract: Obesity and its associated comorbidities are among the most prevalent and challenging conditions confronting the medical profession in the 21st century. A major metabolic consequence of obesity is insulin resistance, which is strongly associated with the deposition of triglycerides in the liver. Hepatic steatosis can either be a benign, noninflammatory condition that appears to have no adverse sequelae or can be associated with steatohepatitis: a condition that can result in end-stage liver disease, accounting for up to 14% of liver transplants in the US. Here we highlight recent advances in our understanding of the molecular events contributing to hepatic steatosis and nonalcoholic steatohepatitis.

1,904 citations

Journal ArticleDOI
TL;DR: To test this hypothesis, peak-to-peak headgroup thicknesses h(pp) of bilayers were obtained from x-ray diffraction of multibilayer arrays at controlled relative humidities and showed that poly-cis unsaturated chain bilayers are thinner and more flexible than saturated/monounsaturated chain Bilayers.

1,725 citations