TitleElevated hepatic fatty acid elongase-5 activity corrects dietary fat-induced hyperglycemia in obese C57BL/6J mice.
Publication TypeJournal Article
Year of Publication2010
AuthorsTripathy S, Torres-Gonzalez M, Jump DB
JournalJ Lipid Res
Date Published2010 Sep
KeywordsAcetyltransferases, Animals, Blood Glucose, Cholesterol, Diet, Dietary Fats, Fatty Acids, Gene Expression Regulation, Gluconeogenesis, Glucose Tolerance Test, Humans, Hyperglycemia, Insulin, Isoenzymes, Liver, Male, Mice, Mice, Inbred C57BL, Mice, Obese, Molecular Sequence Data, Signal Transduction, Triglycerides

Elevated hepatic fatty acid elongase-5 (Elovl5) activity lowers blood glucose in fasted chow-fed C57BL/6J mice. As high-fat diets induce hyperglycemia and suppress hepatic Elovl5 activity, we tested the hypothesis that elevated hepatic Elovl5 expression attenuates hyperglycemia in high-fat-diet-induced obese mice. Increasing hepatic Elovl5 activity by a recombinant adenoviral approach restored blood glucose and insulin, HOMA-IR, and glucose tolerance to normal values in obese mice. Elevated Elovl5 activity increased hepatic content of Elovl5 products (20:3,n-6, 22:4,n-6) and suppressed levels of enzymes (Pck1, G6Pc) and transcription factors (FoxO1 and PGC1alpha, but not CRTC2) involved in gluconeogenesis. Effects of Elovl5 on FoxO1 nuclear abundance correlated with increased phosphorylation of FoxO1, Akt, and the catalytic unit of PP2A, as well as a decline in cellular abundance of TRB3. Such changes are mechanistically linked to the regulation of FoxO1 nuclear abundance and gluconeogenesis. These results show that Elovl5 activity impacts the hepatic abundance and phosphorylation status of multiple proteins involved in gluconeogenesis. Our findings establish a link between fatty acid elongation and hepatic glucose metabolism and suggest a role for regulators of Elovl5 activity in the treatment of diet-induced hyperglycemia.

Alternate JournalJ. Lipid Res.
PubMed ID20488798
PubMed Central IDPMC2918446
Grant ListR01 DK043220 / DK / NIDDK NIH HHS / United States
DK-43220 / DK / NIDDK NIH HHS / United States