Document Detail


CTRP1 protein enhances fatty acid oxidation via AMP-activated protein kinase (AMPK) activation and acetyl-CoA carboxylase (ACC) inhibition.
MedLine Citation:
PMID:  22086915     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We previously described the adipokine CTRP1, which has up-regulated expression following exposure to the anti-diabetic drug rosiglitazone and increased circulating levels in adiponectin-null mice (Wong, G. W., Krawczyk, S. A., Kitidis-Mitrokostas, C., Revett, T., Gimeno, R., and Lodish, H. F. (2008) Biochem. J. 416, 161-177). Although recombinant CTRP1 lowers blood glucose in mice, its physiological function, mechanisms of action, and roles in metabolic stress remain unknown. Here, we show that circulating levels of CTRP1 are strikingly reduced in diet-induced obese mice. Overexpressing CTRP1 in transgenic mice improved insulin sensitivity and decreased high-fat diet-induced weight gain. Reduced adiposity resulted from enhanced fatty acid oxidation and energy expenditure, effects mediated by AMP-activated protein kinase (AMPK). In skeletal muscle of transgenic mice, AMPKα and its downstream target, acetyl-CoA carboxylase (ACC), were hyperphosphorylated, indicative of AMPK activation and ACC inhibition. Inactivation of ACC promotes mitochondrial fat oxidation. Consistent with the direct effect of CTRP1 on AMPK signaling, recombinant CTRP1 administration acutely stimulated muscle AMPKα and ACC phosphorylation in vivo. In isolated soleus muscle, recombinant CTRP1 activated AMPK signaling to increase fatty acid oxidation ex vivo, an effect abrogated by an AMPK inhibitor. These results provide the first in vivo evidence that CTRP1 is a novel regulator of fatty acid metabolism.
Authors:
Jonathan M Peterson; Susan Aja; Zhikui Wei; G William Wong
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-11-15
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  287     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-01-09     Completed Date:  2012-02-27     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1576-87     Citation Subset:  IM    
Affiliation:
Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
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MeSH Terms
Descriptor/Qualifier:
AMP-Activated Protein Kinases / genetics,  metabolism*
Acetyl-CoA Carboxylase / genetics,  metabolism*
Adipokines / genetics,  metabolism*
Adiposity / genetics
Animals
Dietary Fats
Energy Metabolism / physiology*
Fatty Acids / genetics,  metabolism*
Male
Mice
Mice, Transgenic
Muscle Proteins / genetics,  metabolism*
Muscle, Skeletal / metabolism*
Oxidation-Reduction
Signal Transduction / physiology
Grant Support
ID/Acronym/Agency:
DK084171/DK/NIDDK NIH HHS; F32DK084607/DK/NIDDK NIH HHS; P60DK079637/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Adipokines; 0/CTRP1 protein, mouse; 0/Dietary Fats; 0/Fatty Acids; 0/Muscle Proteins; EC 2.7.11.1/AMP-Activated Protein Kinases; EC 6.4.1.2/Acetyl-CoA Carboxylase
Comments/Corrections

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


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