Submitted on March 6, 2008
Revised on March 25, 2008
Accepted on March 29, 2008
Elevated hepatic fatty acid elongase-5 (elovl-5) activity affects multiple pathways controlling hepatic lipid and carbohydrate composition
Yun Wang, Moises Torres-Gonzalez, Sasmita Tripathy, Daniela Botolin, Barbara Christian, and Donald B. Jump
Department of Nutrition and Exercise Science, Oregon State University, Corvallis, OR 97331-5109
Corresponding Author: Donald.Jump{at}oregonstate.edu
Hepatic fatty acid elongase-5 (Elovl-5) plays an important role in long chain mono- and polyunsaturated fatty acid (PUFA) synthesis. Elovl5 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. Adenoviral-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 (20:4,n-6) and docosahexaenoic (22:6,n-3) acid content. The fasting-refeeding response of PPARalpha-regulated genes was attenuated in mice with elevated Elovl5 activity. In contrast, the fasting-refeeding response of hepatic SREBP1- and ChREBP/MLX-regulated genes, Akt and Gsk3beta phosphorylation, and the accumulation of hepatic glycogen content and nuclear SREBP-1 was not impaired by elevated Elovl5 activity. Hepatic triglyceride content and the phosphorylation of AMPK & JNK1/2 were reduced by elevated Elovl5 activity. Hepatic PepCk expression was suppressed, while hepatic glycogen content and phosphorylated Gsk3beta 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 affects multiple pathways regulating hepatic lipid and carbohydrate composition.
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