Document Detail


Elevated hepatic fatty acid elongase-5 activity corrects dietary fat-induced hyperglycemia in obese C57BL/6J mice.
MedLine Citation:
PMID:  20488798     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Sasmita Tripathy; Moises Torres-Gonzalez; Donald B Jump
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2010-05-19
Journal Detail:
Title:  Journal of lipid research     Volume:  51     ISSN:  0022-2275     ISO Abbreviation:  J. Lipid Res.     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-08-12     Completed Date:  2011-02-14     Revised Date:  2012-05-09    
Medline Journal Info:
Nlm Unique ID:  0376606     Medline TA:  J Lipid Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2642-54     Citation Subset:  IM    
Affiliation:
Department of Nutrition and Exercise Sciences, The Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA.
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MeSH Terms
Descriptor/Qualifier:
Acetyltransferases / genetics,  metabolism*
Animals
Blood Glucose / metabolism
Cholesterol / blood
Diet
Dietary Fats* / adverse effects,  metabolism
Fatty Acids / chemistry,  metabolism
Gene Expression Regulation
Gluconeogenesis / physiology
Glucose Tolerance Test
Humans
Hyperglycemia* / etiology,  metabolism
Insulin / blood
Isoenzymes / genetics,  metabolism*
Liver / chemistry,  enzymology*
Male
Mice
Mice, Inbred C57BL
Mice, Obese*
Molecular Sequence Data
Signal Transduction / physiology
Triglycerides / blood
Grant Support
ID/Acronym/Agency:
DK-43220/DK/NIDDK NIH HHS; R01 DK043220/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Blood Glucose; 0/Dietary Fats; 0/Fatty Acids; 0/Insulin; 0/Isoenzymes; 0/Triglycerides; 57-88-5/Cholesterol; EC 2.3.1.-/Acetyltransferases; EC 2.3.1.-/fatty acid elongases
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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