| Elovl5 Regulates the mTORC2-Akt-FOXO1 Pathway by Controlling Hepatic cis-Vaccenic Acid Synthesis in Diet-Induced Obese Mice. | |
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MedLine Citation:
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PMID: 23099444 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Elevated hepatic expression of fatty acid elongase-5 (Elovl5) induces FoxO1 phosphorylation, lowers FoxO1 nuclear content and suppresses expression of genes involved in gluconeogenesis. In this report we define the molecular and metabolic basis of Elovl5 control of FoxO1 phosphorylation. Adenoviral-mediated (Ad-Elovl5) induction of hepatic Elovl5 in diet induced obese-glucose intolerant mice and HepG2 cells increased the phosphorylation of Akt2-S473 (mTORC2 site), but not Akt2-T308 (PDK1 site). The Akt2 inhibitor, Akti1/2, blocked Elovl5 induction of FoxO1-S256 phosphorylation in HepG2 cells. Elevated Elovl5 activity in liver and HepG2 cells induced rictor mRNA, rictor protein and rictor-mTOR interaction, while rictor knockdown (siRNA) attenuated Elovl5 induction of Akt2-S473 and FoxO1-S256 phosphorylation in HepG2 cells. Fatty acid analysis revealed that the abundance of cis-vaccenic acid (18:1,n-7) was increased in livers of obese mice and HepG2 cells following Ad-Elovl5 infection. Treating HepG2 cells with Elovl5 substrates established that palmitoleic acid (16:1,n-7), but not gamma-linolenic acid (18:3,n-6), induced rictor protein, Akt-S473 and FoxO1-S256 phosphorylation. Inhibition of fatty acid elongation blocked 16:1,n-7, but not 18:1,n-7, induction of rictor protein and Akt-S473 and FoxO1-S256 phosphorylation. These results establish a novel link between Elovl5 mediated synthesis of 18:1,n-7 and gluconeogenesis through the control of the mTORC2-Akt-FoxO1 pathway. |
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Authors:
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Sasmita Tripathy; Donald B Jump |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-10-24 |
Journal Detail:
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Title: Journal of lipid research Volume: - ISSN: 0022-2275 ISO Abbreviation: J. Lipid Res. Publication Date: 2012 Oct |
Date Detail:
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Created Date: 2012-10-26 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0376606 Medline TA: J Lipid Res Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Oregon State University, United States. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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