The role of glycerol-3-phosphate dehydrogenase 1 in the progression of fatty liver after acute ethanol administration in mice.
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 (14)C-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.
Laboratory of Nutritional Biochemistry, Graduate School of Nutritional and Environmental Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan. Electronic address: s13220@u-shizuoka-ken.ac.jp.
Tomoki
T
Sato
Laboratory of Nutritional Biochemistry, Graduate School of Nutritional and Environmental Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan. Electronic address: moritaa@u-shizuoka-ken.ac.jp.
Akihito
A
Morita
Department of Biological Science, Graduate School of Science, Osaka Prefecture University, 1-2 Gakuen-cho, Naka-ku, Sakai 599-8570, Japan. Electronic address: morin@b.s.osakafu-u.ac.jp.
Nobuko
N
Mori
Laboratory of Nutritional Biochemistry, Graduate School of Nutritional and Environmental Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan. Electronic address: miura@u-shizuoka-ken.ac.jp.
Shinji
S
Miura
D000818:Animals; D000431:Ethanol / Q000008:administration & dosage / Q000009:adverse effects*; D005234:Fatty Liver / Q000139:chemically induced* / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D017353:Gene Deletion; D005947:Glucose / Q000378:metabolism; D005993:Glycerolphosphate Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics; D014280:Triglycerides / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
D012333:RNA, Messenger; D014280:Triglycerides; D000431:Ethanol; D005993:Glycerolphosphate Dehydrogenase; D005947:Glucose
BALB/cHeA mice; Glycerol-3-phosphate; Glyceroneogenesis; Lipogenesis; Triglyceride synthesis