| SIRT1 deacetylase in SF1 neurons protects against metabolic imbalance. | |
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MedLine Citation:
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PMID: 21907137 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Chronic feeding on high-calorie diets causes obesity and type 2 diabetes mellitus (T2DM), illnesses that affect hundreds of millions. Thus, understanding the pathways protecting against diet-induced metabolic imbalance is of paramount medical importance. Here, we show that mice lacking SIRT1 in steroidogenic factor 1 (SF1) neurons are hypersensitive to dietary obesity owing to maladaptive energy expenditure. Also, mutant mice have increased susceptibility to developing dietary T2DM due to insulin resistance in skeletal muscle. Mechanistically, these aberrations arise, in part, from impaired metabolic actions of the neuropeptide orexin-A and the hormone leptin. Conversely, mice overexpressing SIRT1 in SF1 neurons are more resistant to diet-induced obesity and insulin resistance due to increased energy expenditure and enhanced skeletal muscle insulin sensitivity. Our results unveil important protective roles of SIRT1 in SF1 neurons against dietary metabolic imbalance. |
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Authors:
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Giorgio Ramadori; Teppei Fujikawa; Jason Anderson; Eric D Berglund; Renata Frazao; Shaday Michán; Claudia R Vianna; David A Sinclair; Carol F Elias; Roberto Coppari |
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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: 14 ISSN: 1932-7420 ISO Abbreviation: Cell Metab. Publication Date: 2011 Sep |
Date Detail:
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Created Date: 2011-09-12 Completed Date: 2012-01-20 Revised Date: 2012-05-01 |
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: 301-12 Citation Subset: IM |
Copyright Information:
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Copyright © 2011 Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Internal Medicine, Division of Hypothalamic Research, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Diabetes Mellitus, Type 2 / complications, metabolism*, pathology Diet, High-Fat / adverse effects Dietary Fats / metabolism, pharmacology Energy Metabolism Female Gene Expression Gene Knockdown Techniques Hypothalamus / cytology, drug effects, metabolism* Immunohistochemistry Insulin / metabolism, pharmacology Insulin Resistance Intracellular Signaling Peptides and Proteins / pharmacology* Leptin / pharmacology Mice Mice, Transgenic Motor Activity / drug effects Neurons / cytology, drug effects, metabolism* Neuropeptides / pharmacology* Obesity / complications, metabolism*, pathology Patch-Clamp Techniques Sirtuin 1 / deficiency*, genetics Steroidogenic Factor 1 / genetics, metabolism |
| Grant Support | |
ID/Acronym/Agency:
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AG027916/AG/NIA NIH HHS; AG028730/AG/NIA NIH HHS; DK080836/DK/NIDDK NIH HHS; R01 AG019719/AG/NIA NIH HHS; R01 AG028730/AG/NIA NIH HHS; R01 DK080836-01A2/DK/NIDDK NIH HHS; R01 DK080836-01A2S1/DK/NIDDK NIH HHS; RL1DK081185/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Dietary Fats; 0/Insulin; 0/Intracellular Signaling Peptides and Proteins; 0/Leptin; 0/Neuropeptides; 0/Steroidogenic Factor 1; 0/orexins; EC 3.5.1.-/Sirt1 protein, mouse; EC 3.5.1.-/Sirtuin 1 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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