| Adipocyte NCoR knockout decreases PPARγ phosphorylation and enhances PPARγ activity and insulin sensitivity. | |
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MedLine Citation:
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PMID: 22078880 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Insulin resistance, tissue inflammation, and adipose tissue dysfunction are features of obesity and Type 2 diabetes. We generated adipocyte-specific Nuclear Receptor Corepressor (NCoR) knockout (AKO) mice to investigate the function of NCoR in adipocyte biology, glucose and insulin homeostasis. Despite increased obesity, glucose tolerance was improved in AKO mice, and clamp studies demonstrated enhanced insulin sensitivity in liver, muscle, and fat. Adipose tissue macrophage infiltration and inflammation were also decreased. PPARγ response genes were upregulated in adipose tissue from AKO mice and CDK5-mediated PPARγ ser-273 phosphorylation was reduced, creating a constitutively active PPARγ state. This identifies NCoR as an adaptor protein that enhances the ability of CDK5 to associate with and phosphorylate PPARγ. The dominant function of adipocyte NCoR is to transrepress PPARγ and promote PPARγ ser-273 phosphorylation, such that NCoR deletion leads to adipogenesis, reduced inflammation, and enhanced systemic insulin sensitivity, phenocopying the TZD-treated state. |
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Authors:
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Pingping Li; Wuqiang Fan; Jianfeng Xu; Min Lu; Hiroyasu Yamamoto; Johan Auwerx; Dorothy D Sears; Saswata Talukdar; DaYoung Oh; Ai Chen; Gautam Bandyopadhyay; Miriam Scadeng; Jachelle M Ofrecio; Sarah Nalbandian; Jerrold M Olefsky |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Cell Volume: 147 ISSN: 1097-4172 ISO Abbreviation: Cell Publication Date: 2011 Nov |
Date Detail:
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Created Date: 2011-11-14 Completed Date: 2012-01-17 Revised Date: 2012-04-27 |
Medline Journal Info:
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Nlm Unique ID: 0413066 Medline TA: Cell Country: United States |
Other Details:
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Languages: eng Pagination: 815-26 Citation Subset: IM |
Copyright Information:
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Copyright © 2011 Elsevier Inc. All rights reserved. |
Affiliation:
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Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adipocytes
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metabolism* Animals Co-Repressor Proteins / genetics* Diabetes Mellitus, Type 2 / metabolism*, pathology Diet, High-Fat Insulin Resistance* Male Mice Mice, Inbred C57BL Mice, Knockout Nuclear Receptor Co-Repressor 1 / metabolism* PPAR gamma / antagonists & inhibitors, metabolism* Phosphorylation Thiazolidinediones |
| Grant Support | |
ID/Acronym/Agency:
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DK 074868/DK/NIDDK NIH HHS; DK033651/DK/NIDDK NIH HHS; DK059820/DK/NIDDK NIH HHS; DK063491/DK/NIDDK NIH HHS; P30 DK063491/DK/NIDDK NIH HHS; R01 DK033651/DK/NIDDK NIH HHS; T32 DK007494/DK/NIDDK NIH HHS; U54 HD 012303-25/HD/NICHD NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Co-Repressor Proteins; 0/Ncor1 protein, mouse; 0/Nuclear Receptor Co-Repressor 1; 0/PPAR gamma; 0/Thiazolidinediones |
| Comments/Corrections | |
Comment In:
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Cell. 2011 Nov 11;147(4):717-8
[PMID:
22078871
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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