| Autophagy in hypothalamic AgRP neurons regulates food intake and energy balance. | |
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MedLine Citation:
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PMID: 21803288 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Macroautophagy is a lysosomal degradative pathway that maintains cellular homeostasis by turning over cellular components. Here we demonstrate a role for autophagy in hypothalamic agouti-related peptide (AgRP) neurons in the regulation of food intake and energy balance. We show that starvation-induced hypothalamic autophagy mobilizes neuron-intrinsic lipids to generate endogenous free fatty acids, which in turn regulate AgRP levels. The functional consequences of inhibiting autophagy are the failure to upregulate AgRP in response to starvation, and constitutive increases in hypothalamic levels of pro-opiomelanocortin and its cleavage product α-melanocyte-stimulating hormone that typically contribute to a lean phenotype. We propose a conceptual framework for considering how autophagy-regulated lipid metabolism within hypothalamic neurons may modulate neuropeptide levels to have immediate effects on food intake, as well as long-term effects on energy homeostasis. Regulation of hypothalamic autophagy could become an effective intervention in conditions such as obesity and the metabolic syndrome. |
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Authors:
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Susmita Kaushik; Jose Antonio Rodriguez-Navarro; Esperanza Arias; Roberta Kiffin; Srabani Sahu; Gary J Schwartz; Ana Maria Cuervo; Rajat Singh |
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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 Aug |
Date Detail:
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Created Date: 2011-08-01 Completed Date: 2012-01-05 Revised Date: 2012-09-26 |
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: 173-83 Citation Subset: IM |
Copyright Information:
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Copyright © 2011 Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Agouti-Related Protein
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metabolism* Animals Autophagy / physiology* Cells, Cultured Eating* Energy Metabolism* Fatty Acids / biosynthesis Hypothalamus / metabolism*, physiology Lipids / biosynthesis Male Mice Mice, Inbred C57BL Mice, Knockout Microtubule-Associated Proteins / genetics Neurons / metabolism* Pro-Opiomelanocortin / genetics, metabolism Starvation alpha-MSH / biosynthesis |
| Grant Support | |
ID/Acronym/Agency:
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AG031782/AG/NIA NIH HHS; DK020541/DK/NIDDK NIH HHS; DK026687/DK/NIDDK NIH HHS; DK087776/DK/NIDDK NIH HHS; K01 DK087776-02/DK/NIDDK NIH HHS; K01 DK087776-03/DK/NIDDK NIH HHS; T32AG023475/AG/NIA NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Agouti-Related Protein; 0/Agrp protein, mouse; 0/Atg7 protein, mouse; 0/Fatty Acids; 0/Lipids; 0/Microtubule-Associated Proteins; 581-05-5/alpha-MSH; 66796-54-1/Pro-Opiomelanocortin |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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