Lipin proteins and glycerolipid metabolism: Roles at the ER membrane and beyond

Zhang, Peixiang; Reue, Karen

doi:10.1016/j.bbamem.2017.04.007

Cited by 114 publications

(118 citation statements)

References 135 publications

(253 reference statements)

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“…A large proportion of TAG synthesis occurs at the ER, but these enzymes may also localize to LDs, the mitochondrial membrane, and in the nucleus (Fig. 1) [27]. …”

Section: Overview Of the Glycerol 3-phosphate Pathway For Lipid Symentioning

confidence: 99%

“…LPIN1 is expressed in many human tissues, but the very severe muscle phenotype may relate to the fact that human skeletal muscle has among the highest LPIN1 expression levels, with little or no expression of LPIN2 or LPIN3 [27]. Several pathogenic LPIN1 mutations have been identified, including deletions, nonsense, missense or frame-shift changes in the protein coding sequence.…”

Section: Critical Physiological Roles For Glycerolipid Synthesis Enmentioning

confidence: 99%

“…These models have allowed mechanistic studies that are not feasible in humans and have greatly augmented our understanding of the physiological and cellular roles of these enzymes. Here we summarize key features of these models, and refer the reader to several excellent reviews for additional information [13,27,47,75–79]. …”

Section: Mouse Models To Study the Physiology Of Glycerolipid Metabmentioning

confidence: 99%

“…Both human and mouse skeletal muscle is characterized by altered phospholipid content, which likely influences cellular membranes and may contribute to the impaired muscle function [61,115]. The action of lipin 1 at multiple membrane sites has been recently reviewed [27]. …”

Section: Mouse Models To Study the Physiology Of Glycerolipid Metabmentioning

confidence: 99%

“…Lipin 1 levels and activity are also regulated through mRNA splicing and post-translational mechanisms, which have been reviewed recently [27] and only selected aspects are briefly described here. One of the key mechanisms for regulation of lipin 1 protein function is through reversible protein phosphorylation.…”

Section: Regulation Of Glycerolipid Synthesis Enzymesmentioning

confidence: 99%

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How lipid droplets “TAG” along: Glycerolipid synthetic enzymes and lipid storage

Wang

Airola

Reue

2017

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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Triacylglycerols (TAG) serve as the predominant form of energy storage in mammalian cells, and TAG synthesis influences conditions such as obesity, fatty liver, and insulin resistance. In most tissues, the glycerol 3-phosphate pathway enzymes are responsible for TAG synthesis, and the regulation and function of these enzymes is therefore important for metabolic homeostasis. Here we review the sites and regulation of glycerol-3-phosphate acyltransferase (GPAT), acylglycerol-3-phosphate acyltransferase (AGPAT), lipin/phosphatidic acid phosphatase (PAP), and diacylglycerol acyltransferase (DGAT) enzyme action. We highlight the critical roles that these enzymes play in human health by reviewing Mendelian disorders that result from mutation in the corresponding genes. We also summarize the valuable insights that genetically engineered mouse models have provided into the cellular and physiological roles of GPATs, AGPATs, lipins and DGATs. Finally, we comment on the status and feasibility of therapeutic approaches to metabolic disease that target enzymes of the glycerol 3-phosphate pathway.

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“…A large proportion of TAG synthesis occurs at the ER, but these enzymes may also localize to LDs, the mitochondrial membrane, and in the nucleus (Fig. 1) [27]. …”

Section: Overview Of the Glycerol 3-phosphate Pathway For Lipid Symentioning

confidence: 99%

Section: Critical Physiological Roles For Glycerolipid Synthesis Enmentioning

confidence: 99%

Section: Mouse Models To Study the Physiology Of Glycerolipid Metabmentioning

confidence: 99%

Section: Mouse Models To Study the Physiology Of Glycerolipid Metabmentioning

confidence: 99%

Section: Regulation Of Glycerolipid Synthesis Enzymesmentioning

confidence: 99%

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How lipid droplets “TAG” along: Glycerolipid synthetic enzymes and lipid storage

Wang

Airola

Reue

2017

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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Lipidomic Profiling Reveals the Effect of Egg Components on Nonalcoholic Steatosis in HepG2 Cells and Its Involved Mechanisms

Wang

Hou

et al. 2020

Euro J Lipid Sci & Tech

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Non‐alcoholic fatty liver disease (NAFLD) is a major cause of cardiovascular disease. The relationship between egg consumption and NAFLD is still controversial for its high cholesterol content. In this study, the effects of different egg components (egg white (EW), egg yolk (EY), and whole egg (WE)) on NAFLD are examined using oleic acid (OA)‐induced HepG2 cells with UPLC‐ESI‐MS/MS approach. The results show EY could affect the lipid profile effectively by increasing phosphocholine (PC), phosphatidylglycerol (PG), and carnitine (CAR). Orthogonal projections to latent structures−discriminate analysis (OPLS‐DA) combine with S‐plot analysis select 10, 82, and 20 potential biomarkers in EW, EY, and WE group, respectively. Up‐regulated TG, DG, and down‐regulated lysophosphatidylcholines (lysoPC), lysophosphatidylethanolamine (lysoPE) biomarkers are found in EY group, while down‐regulated TG and FFA are found in EW and WE group. Glycerolipid and choline metabolism are the most involved pathways affected by EY and WE. In addition, the mechanism is associated with the expression of Pla2g15, Pnpla6‐1, Gad1, and involved lipogenic genes ABC1 and PPARα. This study suggests that WE treatment can ameliorate OA‐induced hepatic steatosis by inhibiting TG accumulation, while EY seems slightly accelerate hepatic steatosis. Furthermore, the effects are closely associated with its effects on glycerolipid metabolism.Practical applications: Nonalcoholic fatty liver disease (NAFLD) is a worldwide disease, while the associations between egg consumption and NAFLD are still poorly understood. This study investigates the effects of egg components on NAFLD in oleic acid (OA)‐induced HepG2 cells based on a targeted lipidomics approach. The results indicate that WE (whole egg) treatment could ameliorate OA‐induced hepatic steatosis by inhibiting TG and FFA accumulation, which is closely associated with glycerolipid metabolism. The results provide knowledge and understanding of the effects of egg on NAFLD and involved mechanism, and further provided nutritional guidelines for egg consumption.

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Metabolism of phospholipids in the yeast Schizosaccharomyces pombe

Holic̆

Pokorná

Griač

2019

Yeast

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The fission yeast Schizosaccharomyces pombe is an important model organism for the study of fundamental questions in eukaryotic cell and molecular biology. A plethora of cellular processes are membrane associated and/or dependent on the proper functioning of cellular membranes. Phospholipids are not only the basic building blocks of cellular membranes; they also serve as precursors to numerous signaling molecules.In this review, we describe the biosynthetic pathways leading to major S. pombe phospholipids, how these pathways are regulated, and what is known about degradation and turnover of fission yeast phospholipids. This review also addresses the synthesis, regulation and the role of water-soluble phospholipid precursors. The last chapter of the review is devoted to the use of S. pombe for the biotechnological production of value-added lipid molecules.

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Lipin proteins and glycerolipid metabolism: Roles at the ER membrane and beyond

Cited by 114 publications

References 135 publications

How lipid droplets “TAG” along: Glycerolipid synthetic enzymes and lipid storage

How lipid droplets “TAG” along: Glycerolipid synthetic enzymes and lipid storage

Lipidomic Profiling Reveals the Effect of Egg Components on Nonalcoholic Steatosis in HepG2 Cells and Its Involved Mechanisms

Metabolism of phospholipids in the yeast Schizosaccharomyces pombe

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