| Ablation of steroid receptor coactivator-3 resembles the human CACT metabolic myopathy. | |
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MedLine Citation:
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PMID: 22560224 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Oxidation of lipid substrates is essential for survival in fasting and other catabolic conditions, sparing glucose for the brain and other glucose-dependent tissues. Here we show Steroid Receptor Coactivator-3 (SRC-3) plays a central role in long chain fatty acid metabolism by directly regulating carnitine/acyl-carnitine translocase (CACT) gene expression. Genetic deficiency of CACT in humans is accompanied by a constellation of metabolic and toxicity phenotypes including hypoketonemia, hypoglycemia, hyperammonemia, and impaired neurologic, cardiac and skeletal muscle performance, each of which is apparent in mice lacking SRC-3 expression. Consistent with human cases of CACT deficiency, dietary rescue with short chain fatty acids drastically attenuates the clinical hallmarks of the disease in mice devoid of SRC-3. Collectively, our results position SRC-3 as a key regulator of β-oxidation. Moreover, these findings allow us to consider platform coactivators such as the SRCs as potential contributors to syndromes such as CACT deficiency, previously considered as monogenic. |
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Authors:
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Brian York; Erin L Reineke; Jørn V Sagen; Bryan C Nikolai; Suoling Zhou; Jean-Francois Louet; Atul R Chopra; Xian Chen; Graham Reed; Jeffrey Noebels; Adekunle M Adesina; Hui Yu; Lee-Jun C Wong; Anna Tsimelzon; Susan Hilsenbeck; Robert D Stevens; Brett R Wenner; Olga Ilkayeva; Jianming Xu; Christopher B Newgard; Bert W O'Malley |
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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 metabolism Volume: 15 ISSN: 1932-7420 ISO Abbreviation: Cell Metab. Publication Date: 2012 May |
Date Detail:
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Created Date: 2012-05-07 Completed Date: 2012-10-03 Revised Date: 2013-05-06 |
Medline Journal Info:
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Nlm Unique ID: 101233170 Medline TA: Cell Metab Country: United States |
Other Details:
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Languages: eng Pagination: 752-63 Citation Subset: IM |
Copyright Information:
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Copyright © 2012 Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Carnitine Acyltransferases / deficiency, genetics*, metabolism* Fatty Acids / genetics, metabolism Gene Expression Regulation Humans Hyperammonemia / genetics, metabolism Hypoglycemia / genetics, metabolism Ketosis / genetics, metabolism Lipid Metabolism Male Mice Mice, Transgenic Muscle, Skeletal / metabolism Muscular Diseases / enzymology, genetics*, metabolism* Nuclear Receptor Coactivator 3 / deficiency, genetics*, metabolism* Oxidation-Reduction |
| Grant Support | |
ID/Acronym/Agency:
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P01 HD08818-37/HD/NICHD NIH HHS; P30 DK079638/DK/NIDDK NIH HHS; P30 DK079638-05/DK/NIDDK NIH HHS; P30 HD024064/HD/NICHD NIH HHS; R01 CA112403/CA/NCI NIH HHS; R01 CA112403/CA/NCI NIH HHS; R01 CA112403-07/CA/NCI NIH HHS; R01 DK058242/DK/NIDDK NIH HHS; R01 DK058242-09/DK/NIDDK NIH HHS; R01 HD007857/HD/NICHD NIH HHS; R01 HD008188/HD/NICHD NIH HHS; R01 HD008188-37/HD/NICHD NIH HHS; R01 HD008188-38S1/HD/NICHD NIH HHS; R01 NS029709/NS/NINDS NIH HHS; R01HD8188-38S1/HD/NICHD NIH HHS; U19 DK062434-08/DK/NIDDK NIH HHS; U19 DK62434-08/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Fatty Acids; EC 2.3.1.-/Carnitine Acyltransferases; EC 2.3.1.48/Nuclear Receptor Coactivator 3 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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