| High-fat-diet-induced obesity and heart dysfunction are regulated by the TOR pathway in Drosophila. | |
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MedLine Citation:
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PMID: 21035763 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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High-fat-diet (HFD)-induced obesity is a major contributor to diabetes and cardiovascular disease, but the underlying genetic mechanisms are poorly understood. Here, we use Drosophila to test the hypothesis that HFD-induced obesity and associated cardiac complications have early evolutionary origins involving nutrient-sensing signal transduction pathways. We find that HFD-fed flies exhibit increased triglyceride (TG) fat and alterations in insulin/glucose homeostasis, similar to mammalian responses. A HFD also causes cardiac lipid accumulation, reduced cardiac contractility, conduction blocks, and severe structural pathologies, reminiscent of diabetic cardiomyopathies. Remarkably, these metabolic and cardiotoxic phenotypes elicited by HFD are blocked by inhibiting insulin-TOR signaling. Moreover, reducing insulin-TOR activity (by expressing TSC1-2, 4EBP or FOXO), or increasing lipase expression-only within the myocardium-suffices to efficiently alleviate cardiac fat accumulation and dysfunction induced by HFD. We conclude that deregulation of insulin-TOR signaling due to a HFD is responsible for mediating the detrimental effects on metabolism and heart function. |
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Authors:
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Ryan T Birse; Joan Choi; Kathryn Reardon; Jessica Rodriguez; Suzanne Graham; Soda Diop; Karen Ocorr; Rolf Bodmer; Sean Oldham |
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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: 12 ISSN: 1932-7420 ISO Abbreviation: Cell Metab. Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-11-01 Completed Date: 2011-03-10 Revised Date: 2012-01-18 |
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: 533-44 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Elsevier Inc. All rights reserved. |
Affiliation:
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NASCR Center, Sanford/Burnham Medical Research Institute, La Jolla, CA 92037, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Dietary Fats / adverse effects* Drosophila / genetics, metabolism* Drosophila Proteins / genetics, metabolism* Heart / physiopathology Heart Diseases / complications, etiology*, metabolism Humans Insulin / metabolism Metabolic Diseases / genetics Mutation Obesity / complications, etiology*, metabolism Phenotype Signal Transduction TOR Serine-Threonine Kinases / genetics, metabolism* Triglycerides / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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P01 AG033561-01A2/AG/NIA NIH HHS; R01 HL054732-10A1/HL/NHLBI NIH HHS; R01 HL084949-01/HL/NHLBI NIH HHS; R01 HL084949-02/HL/NHLBI NIH HHS; R01 HL084949-03/HL/NHLBI NIH HHS; R01 HL084949-04/HL/NHLBI NIH HHS; R01 HL085481-02/HL/NHLBI NIH HHS; R01 HL085481-05/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Dietary Fats; 0/Drosophila Proteins; 0/Insulin; 0/Triglycerides; EC 2.7.1.1/TOR Serine-Threonine Kinases |
| Comments/Corrections | |
Comment In:
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Expert Rev Cardiovasc Ther. 2011 Mar;9(3):299-302
[PMID:
21438808
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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