Elevated hepatic fatty acid elongase-5 activity affects multiple pathways controlling hepatic lipid and carbohydrate composition.
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.
Wang
Yun
Y
Department of Physiology, Michigan State University, East Lansing, MI 48824, USA.
Torres-Gonzalez
Moises
M
Tripathy
Sasmita
S
Botolin
Daniela
D
Christian
Barbara
B
Jump
Donald B
DB
D000123:Acetyltransferases / Q000378:metabolism*; D000818:Animals; D050260:Carbohydrate Metabolism; D002478:Cells, Cultured; D000081031:Fatty Acid Elongases; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D050356:Lipid Metabolism; D008099:Liver / Q000201:enzymology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D047493:PPAR alpha / Q000378:metabolism; D051381:Rats
C000630954:ELOVL5 protein, human; D047493:PPAR alpha; D000123:Acetyltransferases; C581235:Elovl5 protein, mouse; D000081031:Fatty Acid Elongases