Document Detail


Autophagy in hypothalamic AgRP neurons regulates food intake and energy balance.
MedLine Citation:
PMID:  21803288     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Susmita Kaushik; Jose Antonio Rodriguez-Navarro; Esperanza Arias; Roberta Kiffin; Srabani Sahu; Gary J Schwartz; Ana Maria Cuervo; Rajat Singh
Related Documents :
24630938 - Differential influence of the 5-httlpr genotype, neuroticism and real-life acute stress...
7943588 - Functional outcome in handsewn versus stapled ileal pouch-anal anastomosis.
22248568 - Does a temperate ungulate that breeds in summer exhibit rut-induced hypophagia? analysi...
6166998 - Molecular structure and mechanical properties of keratins.
24479448 - Nutritional quality of the school-day diet in irish children (5-12 years).
23046858 - Occurrence and exposure assessment of aflatoxins in catalonia (spain).
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cell metabolism     Volume:  14     ISSN:  1932-7420     ISO Abbreviation:  Cell Metab.     Publication Date:  2011 Aug 
Date Detail:
Created Date:  2011-08-01     Completed Date:  2012-01-05     Revised Date:  2014-10-19    
Medline Journal Info:
Nlm Unique ID:  101233170     Medline TA:  Cell Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  173-83     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Elsevier Inc. All rights reserved.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Agouti-Related Protein / 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:
AG031782/AG/NIA NIH HHS; DK020541/DK/NIDDK NIH HHS; DK026687/DK/NIDDK NIH HHS; DK087776/DK/NIDDK NIH HHS; K01 DK087776/DK/NIDDK NIH HHS; K01 DK087776-02/DK/NIDDK NIH HHS; P30 AG038072/AG/NIA NIH HHS; T32AG023475/AG/NIA NIH HHS
Chemical
Reg. No./Substance:
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


Previous Document:  Histone Demethylase UTX-1 Regulates C. elegans Life Span by Targeting the Insulin/IGF-1 Signaling P...
Next Document:  Deletion of the mammalian INDY homolog mimics aspects of dietary restriction and protects against ad...