Document Detail


VASP increases hepatic fatty acid oxidation by activating AMPK in mice.
MedLine Citation:
PMID:  23349495     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Activation of AMP-activated protein kinase (AMPK) signaling reduces hepatic steatosis and hepatic insulin resistance; however, its regulatory mechanisms are not fully understood. In this study, we sought to determine whether vasodilator-stimulated phosphoprotein (VASP) signaling improves lipid metabolism in the liver and, if so, whether VASP's effects are mediated by AMPK. We show that disruption of VASP results in significant hepatic steatosis as a result of significant impairment of fatty acid oxidation, VLDL-triglyceride (TG) secretion, and AMPK signaling. Overexpression of VASP in hepatocytes increased AMPK phosphorylation and fatty acid oxidation and reduced hepatocyte TG accumulation; however, these responses were suppressed in the presence of an AMPK inhibitor. Restoration of AMPK phosphorylation by administration of 5-aminoimidazole-4-carboxamide riboside in Vasp(-/-) mice reduced hepatic steatosis and normalized fatty acid oxidation and VLDL-TG secretion. Activation of VASP by the phosphodiesterase-5 inhibitor, sildenafil, in db/db mice reduced hepatic steatosis and increased phosphorylated (p-)AMPK and p-acetyl CoA carboxylase. In Vasp(-/-) mice, however, sildendafil treatment did not increase p-AMPK or reduce hepatic TG content. These studies identify a role of VASP to enhance hepatic fatty acid oxidation by activating AMPK and to promote VLDL-TG secretion from the liver.
Authors:
Sanshiro Tateya; Norma Rizzo-De Leon; Priya Handa; Andrew M Cheng; Vicki Morgan-Stevenson; Kayoko Ogimoto; Jenny E Kanter; Karin E Bornfeldt; Guenter Daum; Alexander W Clowes; Alan Chait; Francis Kim
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2013-01-24
Journal Detail:
Title:  Diabetes     Volume:  62     ISSN:  1939-327X     ISO Abbreviation:  Diabetes     Publication Date:  2013 Jun 
Date Detail:
Created Date:  2013-05-24     Completed Date:  2013-08-02     Revised Date:  2014-03-19    
Medline Journal Info:
Nlm Unique ID:  0372763     Medline TA:  Diabetes     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1913-22     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
AMP-Activated Protein Kinases / metabolism*
Aminoimidazole Carboxamide / analogs & derivatives,  pharmacology
Animals
Blotting, Western
Cell Adhesion Molecules / genetics,  metabolism*
Fatty Acids / metabolism*
Liver / enzymology*,  metabolism*
Mice
Mice, Mutant Strains
Microfilament Proteins / genetics,  metabolism*
Oxidation-Reduction
Phosphoproteins / genetics,  metabolism*
Phosphorylation / drug effects
Reverse Transcriptase Polymerase Chain Reaction
Ribonucleosides / pharmacology
Grant Support
ID/Acronym/Agency:
DK-073878/DK/NIDDK NIH HHS; HL-062887/HL/NHLBI NIH HHS; HL-097365/HL/NHLBI NIH HHS; HL-92969/HL/NHLBI NIH HHS; HL-94352/HL/NHLBI NIH HHS; P30 DK-035816/DK/NIDDK NIH HHS; R01 HL062887/HL/NHLBI NIH HHS; T32 HL-07828/HL/NHLBI NIH HHS; T32 HL007828/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Cell Adhesion Molecules; 0/Fatty Acids; 0/Microfilament Proteins; 0/Phosphoproteins; 0/Ribonucleosides; 0/vasodilator-stimulated phosphoprotein; 360-97-4/Aminoimidazole Carboxamide; 53IEF47846/acadesine; EC 2.7.11.1/AMP-Activated Protein Kinases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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