Regulation of the Fatty Acid Synthase Promoter by Insulin

• Published in: The Journal of nutrition Vol. 130; no. 2; pp. 315 - 320S
• Main Authors: Sul, Hei Sook, Latasa, Maria-Jesus, Moon, Yangsoo, Kim, Kee-Hong
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Bethesda, MD American Society for Nutritional Sciences 01.02.2000; American Institute of Nutrition
• Subjects: adipocytes; Animals; biochemical pathways; Biological and medical sciences; diet; Enzymes; Fasting - metabolism; Fatty Acid Synthases - genetics; Fatty Acid Synthases - physiology; Fatty acids; Fatty Acids - biosynthesis; Fundamental and applied biological sciences. Psychology; gene expression; Gene Expression Regulation, Enzymologic; Genes; glycerol-3-phosphate acyltransferase; Glycerol-3-Phosphate O-Acyltransferase - biosynthesis; Insulin; Insulin - physiology; insulin secretion; Lipids. Glycolipids; Liver - enzymology; Liver - metabolism; Metabolisms and neurohumoral controls; mitochondria; Mitochondria - enzymology; Mitochondria - metabolism; Nutrition; promoter regions; reporter genes; Signal Transduction - physiology; transcription (genetics); Vertebrates: anatomy and physiology, studies on body, several organs or systems; Acyltransferases; Pancreatic hormone; Enzyme; Transcription promoter; Transferases; Hormonal regulation; Lipids; Metabolism; Fatty acids; Insulin; Fatty-acid synthase
• ISSN: 0022-3166; 1541-6100
• DOI: 10.1093/jn/130.2.315S

Expression of critical enzymes in fatty acid and fat biosynthesis is tightly controlled by nutritional and hormonal stimuli. The expression of fatty acid synthase, which catalyzes all reactions for synthesis of palmitate from acetyl-CoA and malonyl-CoA, and of mitochondrial glycerol-3-phosphate acyltransferase, which catalyzes the first acylation step in glycerophospholipid synthesis, is decreased to an undetectable level during fasting. Food intake, especially a high carbohydrate, fat-free diet after fasting, causes a dramatic increase in the transcription of these genes. Insulin secretion is increased during feeding and has a positive effect on expression. By using adipocytes in culture and transgenic mice that express the reporter gene driven by the fatty acid synthase promoter, the cis-acting sequence that mediates insulin regulation of the fatty acid synthase promoter was defined. Upstream stimulatory factors (USF) that bind to the -65 E-box are required for insulin-mediated transcriptional activation of the fatty acid symthase gene. Sterol regulatory element binding protein (SREBP)-1 may be also involved in induction of these genes during feeding. Using specific inhibitors and expressing various signaling molecules, we found that insulin regulation of the fatty acid synthase promoter is mediated by the phosphatidylinositol (PI)3-kinase signaling pathway and that protein kinase B/akt is a downstream effector.