TitleElevated hepatic fatty acid elongase-5 activity affects multiple pathways controlling hepatic lipid and carbohydrate composition.
Publication TypeJournal Article
Year of Publication2008
AuthorsWang, Y, Torres-Gonzalez, M, Tripathy, S, Botolin, D, Christian, B, Jump, DB
JournalJ Lipid Res
Date Published2008 Jul
KeywordsAcetyltransferases, Animals, Carbohydrate Metabolism, Cells, Cultured, Gene Expression Regulation, Enzymologic, Humans, Lipid Metabolism, Liver, Male, Mice, Mice, Inbred C57BL, PPAR alpha, Rats


Hepatic fatty acid elongase-5 (Elovl-5) plays an important role in long chain monounsaturated and polyunsaturated fatty acid synthesis. Elovl-5 activity is regulated during development, by diet, hormones, and drugs, and in chronic disease. This report examines the impact of elevated Elovl-5 activity on hepatic function. Adenovirus-mediated induction of Elovl5 activity in livers of C57BL/6 mice increased hepatic and plasma levels of dihomo-gamma-linolenic acid (20:3,n-6) while suppressing hepatic arachidonic acid (20:4,n-6) and docosahexaenoic acid (22:6,n-3) content. The fasting-refeeding response of peroxisome proliferator-activated receptor alpha-regulated genes was attenuated in mice with elevated Elovl5 activity. In contrast, the fasting-refeeding response of hepatic sterol-regulatory element binding protein-1 (SREBP-1)-regulated and carbohydrate-regulatory element binding protein/Max-like factor X-regulated genes, Akt and glycogen synthase kinase (Gsk)-3beta phosphorylation, and the accumulation of hepatic glycogen content and nuclear SREBP-1 were not impaired by elevated Elovl5 activity. Hepatic triglyceride content and the phosphorylation of AMP-activated kinase alpha and Jun kinase 1/2 were reduced by elevated Elovl5 activity. Hepatic phosphoenolpyruvate carboxykinase expression was suppressed, while hepatic glycogen content and phosphorylated Gsk-3beta were significantly increased, in livers of fasted mice with increased Elovl5 activity. As such, hepatic Elovl5 activity may affect hepatic glucose production during fasting. In summary, Elovl5-induced changes in hepatic fatty acid content affect multiple pathways regulating hepatic lipid and carbohydrate composition.

Alternate JournalJ. Lipid Res.
PubMed ID18376007
PubMed Central IDPMC2431109
Grant ListR01 DK043220 / DK / NIDDK NIH HHS / United States
DK-43220 / DK / NIDDK NIH HHS / United States