The role of glycerol-3-phosphate dehydrogenase 1 in the progression of fatty liver after acute ethanol administration in mice |
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Authors: | Tomoki Sato Akihito Morita Nobuko Mori Shinji Miura |
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Institution: | 1. Laboratory of Nutritional Biochemistry, Graduate School of Nutritional and Environmental Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan;2. Department of Biological Science, Graduate School of Science, Osaka Prefecture University, 1-2 Gakuen-cho, Naka-ku, Sakai 599-8570, Japan |
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Abstract: | Acute ethanol consumption leads to the accumulation of triglycerides (TGs) in hepatocytes. The increase in lipogenesis and reduction of fatty acid oxidation are implicated as the mechanisms underlying ethanol-induced hepatic TG accumulation. Although glycerol-3-phosphate (Gro3P), formed by glycerol kinase (GYK) or glycerol-3-phosphate dehydrogenase 1 (GPD1), is also required for TG synthesis, the roles of GYK and GPD1 have been the subject of some debate. In this study, we examine (1) the expression of genes involved in Gro3P production in the liver of C57BL/6J mice in the context of hepatic TG accumulation after acute ethanol intake, and (2) the role of GPD1 in the progression of ethanol-induced fatty liver using GPD1 null mice. As a result, in C57BL/6J mice, ethanol-induced hepatic TG accumulation began within 2 h and was 1.7-fold greater than that observed in the control group after 6 h. The up-regulation of GPD1 began 2 h after administering ethanol, and significantly increased 6 h later with the concomitant escalation in the glycolytic gene expression. The incorporation of 14C-labelled glucose into TG glycerol moieties increased during the same period. On the other hand, in GPD1 null mice carrying normal GYK activity, no significant increase in hepatic TG level was observed after acute ethanol intake. In conclusion, GPD1 and glycolytic gene expression is up-regulated by ethanol, and GPD1-mediated incorporation of glucose into TG glycerol moieties together with increased lipogenesis, is suggested to play an important role in ethanol-induced hepatic TG accumulation. |
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Keywords: | ChREBP carbohydrate response element-binding protein DGAT acyl-CoA:diacylglycerol acyltransferase DHAP dehydroxyacetone phosphate FAS fatty acid synthase Foxo1 forkhead box O1 GAPDH glyceraldehyde-3-phosphate dehydrogenase GPD1 glycerol-3-phosphate dehydrogenase 1 Gro3P glycerol-3-phosphate GYK glycerol kinase NADH reduced nicotinamide adenine dinucleotide NAD+ oxidized nicotinamide adenine dinucleotide NADPH nicotinamide adenine dinucleotide phosphate PEPCK phosphoenolpyruvate carboxykinase PFKL liver phosphofructokinase PGC-1 alpha peroxisome proliferator-activated receptor gamma coactivator 1 alpha PPAR peroxisome proliferator-activated receptor PYGL liver glycogen phosphorylase SREBP-1c sterol regulatory element-binding protein-1c TG triglyceride |
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