Document Detail


Thyroid hormone stimulates hepatic lipid catabolism via activation of autophagy.
MedLine Citation:
PMID:  22684107     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
For more than a century, thyroid hormones (THs) have been known to exert powerful catabolic effects, leading to weight loss. Although much has been learned about the molecular mechanisms used by TH receptors (TRs) to regulate gene expression, little is known about the mechanisms by which THs increase oxidative metabolism. Here, we report that TH stimulation of fatty acid β-oxidation is coupled with induction of hepatic autophagy to deliver fatty acids to mitochondria in cell culture and in vivo. Furthermore, blockade of autophagy by autophagy-related 5 (ATG5) siRNA markedly decreased TH-mediated fatty acid β-oxidation in cell culture and in vivo. Consistent with this model, autophagy was altered in livers of mice expressing a mutant TR that causes resistance to the actions of TH as well as in mice with mutant nuclear receptor corepressor (NCoR). These results demonstrate that THs can regulate lipid homeostasis via autophagy and help to explain how THs increase oxidative metabolism.
Authors:
Rohit Anthony Sinha; Seo-Hee You; Jin Zhou; Mobin M Siddique; Boon-Huat Bay; Xuguang Zhu; Martin L Privalsky; Sheue-Yann Cheng; Robert D Stevens; Scott A Summers; Christopher B Newgard; Mitchell A Lazar; Paul M Yen
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-06-11
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  122     ISSN:  1558-8238     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-07-03     Completed Date:  2012-09-11     Revised Date:  2013-07-12    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2428-38     Citation Subset:  AIM; IM    
Affiliation:
Cardiovascular and Metabolic Disorders Program, Duke-NUS Graduate Medical School, Singapore.
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MeSH Terms
Descriptor/Qualifier:
Animals
Autophagy
Carnitine / analogs & derivatives,  metabolism
Cell Line, Tumor
Fatty Acids / metabolism
Gene Expression Profiling
Gene Knockdown Techniques
Hepatocytes / metabolism,  physiology,  ultrastructure
Histone Deacetylases / metabolism
Humans
Ketone Bodies / metabolism
Lipid Metabolism*
Liver / metabolism*
Male
Metabolic Networks and Pathways / genetics
Metabolome
Mice
Mice, Inbred C57BL
Microtubule-Associated Proteins / genetics,  metabolism
Nuclear Receptor Co-Repressor 1 / metabolism
Oligonucleotide Array Sequence Analysis
Oxidation-Reduction
Phagosomes / metabolism
Protein Binding
RNA Interference
Receptors, Thyroid Hormone / metabolism
Triiodothyronine / physiology*
Grant Support
ID/Acronym/Agency:
DK 43806/DK/NIDDK NIH HHS; U19DK/HL/ES 62434/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Atg5 protein, mouse; 0/Fatty Acids; 0/Ketone Bodies; 0/Microtubule-Associated Proteins; 0/Nuclear Receptor Co-Repressor 1; 0/Receptors, Thyroid Hormone; 0/acylcarnitine; 0/light chain 3, human; 541-15-1/Carnitine; 6893-02-3/Triiodothyronine; EC 3.5.1.98/Histone Deacetylases; EC 3.5.1.98/histone deacetylase 3
Comments/Corrections

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


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