Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015695 (fatty liver)
 13,941 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glycerol-3-phosphate acyltransferases (GPATs; EC2.3.1.15) catalyze the first step in the de novo synthesis of neutral lipids (triglycerides) and glycerophospholipids. The existence of multiple enzyme isoforms with GPAT activity was predicted many years ago when GPAT activities with distinct kinetic profiles and sensitivity to inhibitors were characterized in two subcellular compartments, mitochondria and microsomes. We now know that mammals have at least four GPAT isoforms with distinct tissue distribution and function. GPAT1 is the major mitochondrial GPAT isoform and is characterized by its resistance to sulfhydryl-modifying reagents, such as N-ethylmaleimide (NEM). GPAT2 is a minor NEM-sensitive mitochondrial isoform. The activity referred to as microsomal GPAT is encoded by two closely related genes, GPAT3 and GPAT4. GPAT isoforms are important regulators of cellular triglyceride and phospholipid content, and may channel fatty acids toward particular metabolic fates. Overexpression and knock-out studies suggest that GPAT isoforms can play important roles in the development of hepatic steatosis, insulin resistance, and obesity; GPAT isoforms are also important for lactation. This review summarizes the current state of knowledge on mammalian GPAT isoforms.
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PMID:Thematic review series: glycerolipids. Mammalian glycerol-3-phosphate acyltransferases: new genes for an old activity. 1865 43

Glycerol-3-phosphate acyltransferase (GPAT) is the rate-limiting enzyme in the de novo pathway of glycerolipid synthesis. It catalyzes the conversion of glycerol-3-phosphate and long-chain acyl-CoA to lysophosphatidic acid. In mammals, four isoforms of GPATs have been identified based on subcellular localization, substrate preferences, and NEM sensitivity, and they have been classified into two groups, one including GPAT1 and GPAT2, which are localized in the mitochondrial outer membrane, and the other including GPAT3 and GPAT4, which are localized in the endoplasmic reticulum membrane. GPATs play a pivotal role in the regulation of triglyceride and phospholipid synthesis. Through gain-of-function and loss-of-function experiments, it has been confirmed that GPATs play a critical role in the development of obesity, hepatic steatosis, and insulin resistance. In line with this, the role of GPATs in metabolism was supported by studies using a GPAT inhibitor, FSG67. Additionally, the functional characteristics of GPATs and the relation between three isoforms (GPAT1, 3, and 4) and insulin resistance has been described in this review.
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PMID:Update on glycerol-3-phosphate acyltransferases: the roles in the development of insulin resistance. 2979 6

Non-alcoholic fatty liver disease (NAFLD) represents a wide spectrum of disease, ranging from simple fatty liver through steatosis with inflammation and necrosis to cirrhosis. One of the most challenging problems in biomedical research and within the chemical industry is to understand the underlying mechanisms of complex disease, and complex adverse outcome pathways (AOPs). Based on a set of 28 steatotic chemicals with gene expression data measured on primary hepatocytes at three times (2, 8, and 24 h) and three doses (low, medium, and high), we identified genes and pathways, defined as molecular initiating events (MIEs) and key events (KEs) of steatosis using a combination of a time series and pathway analyses. Among the genes deregulated by these compounds, the study highlighted OSBPL9, ALDH7A1, MYADM, SLC51B, PRDX6, GPAT3, TMEM135, DLGDA5, BCO2, APO10LA, TSPAN6, NEURL1B, and DUSP1. Furthermore, pathway analysis indicated deregulation of pathways related to lipid accumulation, such as fat digestion and absorption, linoleic and linolenic acid metabolism, calcium signaling pathway, fatty acid metabolism, peroxisome, retinol metabolism, and steroid metabolic pathways in a time dependent manner. Such transcription profile analysis can help in the understanding of the steatosis evolution over time generated by chemical exposure.
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PMID:Analysis of Time-Series Gene Expression Data to Explore Mechanisms of Chemical-Induced Hepatic Steatosis Toxicity. 3027 2