The role of glycerol-3-phosphate dehydrogenase 1 in the progression of fatty liver after acute ethanol administration in mice

• Published in: Biochemical and biophysical research communications Vol. 444; no. 4; pp. 525 - 530
• Main Authors: Sato, Tomoki, Morita, Akihito, Mori, Nobuko, Miura, Shinji
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 21.02.2014
• Subjects: 60 APPLIED LIFE SCIENCES; alcohol abuse; Animals; BALB/cHeA mice; beta oxidation; CARBOXYLIC ACIDS; ETHANOL; Ethanol - administration & dosage; Ethanol - adverse effects; fatty liver; Fatty Liver - chemically induced; Fatty Liver - enzymology; Fatty Liver - genetics; Fatty Liver - pathology; Gene Deletion; gene expression; GENES; GLUCOSE; Glucose - metabolism; GLYCEROL; glycerol kinase; Glycerol-3-phosphate; glycerol-3-phosphate dehydrogenase; Glycerolphosphate Dehydrogenase - genetics; Glycerolphosphate Dehydrogenase - metabolism; Glyceroneogenesis; GLYCOGEN; glycolysis; hepatocytes; INTAKE; Lipogenesis; LIVER; Liver - drug effects; Liver - enzymology; Liver - metabolism; Liver - pathology; LIVER CELLS; MESSENGER-RNA; MICE; Mice, Inbred BALB C; Mice, Inbred C57BL; NADH2; NADP; OXIDATION; PHOSPHATES; PHOSPHOENOLPYRUVATE; RECEPTORS; RNA, Messenger - genetics; STEROLS; triacylglycerols; Triglyceride synthesis; TRIGLYCERIDES; Triglycerides - metabolism; Up-Regulation - drug effects; NADPH; BALB/cHeA mice; Glyceroneogenesis; PEPCK; PGC-1 alpha; Triglyceride synthesis; DGAT; PYGL; DHAP; SREBP-1c; NAD; ChREBP; PFKL; NADH; TG; PPAR; Glycerol-3-phosphate; GPD1; GYK; FAS; Gro3P; Lipogenesis; GAPDH; Foxo1
• ISSN: 0006-291X; 1090-2104; 1090-2104
• DOI: 10.1016/j.bbrc.2014.01.096

•Ethanol administration increased GPD1 mRNA expression.•Ethanol administration increased glucose incorporation into TG glycerol moieties.•No increase in hepatic TG levels was observed in ethanol-injected GPD1 null mice.•We propose that GPD1 is required for ethanol-induced TG accumulation in the liver. 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 2h and was 1.7-fold greater than that observed in the control group after 6h. The up-regulation of GPD1 began 2h after administering ethanol, and significantly increased 6h 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.