Document Detail


Targeted deletion of thioesterase superfamily member 1 promotes energy expenditure and protects against obesity and insulin resistance.
MedLine Citation:
PMID:  22427358     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Mammalian acyl-CoA thioesterases (Acots) catalyze the hydrolysis of fatty acyl-CoAs to form free fatty acids plus CoA, but their metabolic functions remain undefined. Thioesterase superfamily member 1 (Them1; synonyms Acot11, StarD14, and brown fat inducible thioesterase) is a long-chain fatty acyl-CoA thioesterase that is highly expressed in brown adipose tissue and is regulated by both ambient temperature and food consumption. Here we show that Them1(-/-) mice were resistant to diet-induced obesity despite greater food consumption. Them1(-/-) mice exhibited increased O(2) consumption and heat production, which were accompanied by increased rates of fatty acid oxidation in brown adipose tissue and up-regulation of genes that promote energy expenditure. Them1(-/-) mice were also protected against diet-induced inflammation in white adipose tissue, as well as hepatic steatosis, and demonstrated improved glucose homeostasis. The absence of Them1 expression in vivo and in cell culture led to markedly attenuated diet- or chemically induced endoplasmic reticulum stress responses, providing a mechanism by which Them1 deficiency protects against insulin resistance and lipid deposition. Taken together, these data suggest that Them1 functions to decrease energy consumption and conserve calories. In the setting of nutritional excess, the overproduction of free fatty acids by Them1 provokes insulin resistance that is associated with inflammation and endoplasmic reticulum stress.
Authors:
Yongzhao Zhang; Yingxia Li; Michele W Niepel; Yuki Kawano; Shuxin Han; Sihao Liu; Alessandro Marsili; P Reed Larsen; Chih-Hao Lee; David E Cohen
Related Documents :
3068808 - Hepatobiliary effects of obesity and weight-reducing surgery.
22289788 - Combination of fucoxanthin and conjugated linoleic acid attenuates body weight gain and...
8485178 - Orally administered gallbladder therapeutic agents, part 1: chenix (chenodeoxycholic ac...
22688548 - Reducing the glycemic index or carbohydrate content of mixed meals reduces postprandial...
936958 - The influence of a chemical diet on the intestinal mucosa after jejuno-ileal bypass in ...
18807108 - Six weeks phylloquinone supplementation produces undesirable effects on blood lipids wi...
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-03-16
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  109     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-04-04     Completed Date:  2012-05-21     Revised Date:  2014-03-19    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  5417-22     Citation Subset:  IM    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Energy Metabolism*
Fatty Acids / metabolism
Gene Deletion*
Insulin Resistance*
Mice
Mice, Knockout
Obesity / prevention & control*
Oxidation-Reduction
Palmitoyl-CoA Hydrolase / genetics*
Grant Support
ID/Acronym/Agency:
5P30 DK36836/DK/NIDDK NIH HHS; DK36256/DK/NIDDK NIH HHS; DK48873/DK/NIDDK NIH HHS; DK56626/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; U24 DK76169/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Fatty Acids; EC 3.1.2.-/Thea protein, mouse; EC 3.1.2.2/Palmitoyl-CoA Hydrolase
Comments/Corrections

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


Previous Document:  Using sketch-map coordinates to analyze and bias molecular dynamics simulations.
Next Document:  Mitofusin 2 (Mfn2) links mitochondrial and endoplasmic reticulum function with insulin signaling and...