Document Detail


Thioesterase superfamily member 2/acyl-CoA thioesterase 13 (Them2/Acot13) regulates hepatic lipid and glucose metabolism.
MedLine Citation:
PMID:  22345407     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Members of the acyl-CoA thioesterase (Acot) gene family catalyze the hydrolysis of fatty acyl-CoAs, but their biological functions remain unknown. Thioesterase superfamily member 2 (Them2; synonym Acot13) is a broadly expressed mitochondria-associated Acot. Them2 was previously identified as an interacting protein of phosphatidylcholine transfer protein (PC-TP). Pctp(-/-) mice exhibit altered fatty acid metabolism that is accompanied by reduced hepatic glucose production. To examine the role of Them2 in regulating hepatic lipid and glucose homeostasis, we generated Them2(-/-) mice. In livers of Them2(-/-) mice compared with Them2(+/+) controls, a 1.9-fold increase in the K(m) of mitochondrial thioesterase activity was accompanied by a 28% increase in fatty acyl-CoA concentration. A reciprocal 23% decrease in free fatty acid concentration was associated with reduced activation of peroxisome proliferator-activated receptor α. However, fatty acid oxidation rates were preserved in livers of Them2(-/-) mice, suggesting that Them2 functions to limit β-oxidation. Hepatic glucose production was also decreased by 45% in the setting of reduced hepatocyte nuclear factor 4α (HNF4α) expression. When fed a high-fat diet, Them2(-/-) mice were resistant to increases in hepatic glucose production and steatosis. These findings reveal key roles for Them2 in the regulation of hepatic metabolism, which are potentially mediated by PC-TP-Them2 interactions.
Authors:
Hye Won Kang; Michele W Niepel; Shuxin Han; Yuki Kawano; David E Cohen
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-02-17
Journal Detail:
Title:  FASEB journal : official publication of the Federation of American Societies for Experimental Biology     Volume:  26     ISSN:  1530-6860     ISO Abbreviation:  FASEB J.     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-05-01     Completed Date:  2012-06-29     Revised Date:  2014-03-19    
Medline Journal Info:
Nlm Unique ID:  8804484     Medline TA:  FASEB J     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2209-21     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Base Sequence
Body Weight
DNA Primers
Energy Metabolism
Enzyme-Linked Immunosorbent Assay
Glucose / metabolism*
Lipid Metabolism*
Liver / metabolism*
Male
Mice
Mice, Knockout
Real-Time Polymerase Chain Reaction
Thiolester Hydrolases / genetics,  metabolism*
Grant Support
ID/Acronym/Agency:
DK-48873/DK/NIDDK NIH HHS; DK-56626/DK/NIDDK NIH HHS; P30 DK034854/DK/NIDDK NIH HHS; P30 DK34854/DK/NIDDK NIH HHS; R01 DK048873/DK/NIDDK NIH HHS; R01 DK056626/DK/NIDDK NIH HHS; R37 DK048873/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/DNA Primers; EC 3.1.2.-/Acot13 protein, mouse; EC 3.1.2.-/Thiolester Hydrolases; IY9XDZ35W2/Glucose
Comments/Corrections

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


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