Document Detail

A central role for neuronal AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) in high-protein diet-induced weight loss.
MedLine Citation:
PMID:  18057094     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: A high-protein diet (HPD) is known to promote the reduction of body fat, but the mechanisms underlying this change are unclear. AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) function as majors regulators of cellular metabolism that respond to changes in energy status, and recent data demonstrated that they also play a critical role in systemic energy balance. Here, we sought to determine whether the response of the AMPK and mTOR pathways could contribute to the molecular effects of an HPD. RESEARCH DESIGN AND METHODS: Western blotting, confocal microscopy, chromatography, light microscopy, and RT-PCR assays were combined to explore the anorexigenic effects of an HPD. RESULTS: An HPD reduced food intake and induced weight loss in both normal rats and ob/ob mice. The intracerebroventricular administration of leucine reduced food intake, and the magnitude of weight loss and reduction of food intake in a leucine-supplemented diet are similar to that achieved by HPD in normal rats and in ob/ob mice, suggesting that leucine is a major component of the effects of an HPD. Leucine and HPD decrease AMPK and increase mTOR activity in the hypothalamus, leading to inhibition of neuropeptide Y and stimulation of pro-opiomelanocortin expression. Consistent with a cross-regulation between AMPK and mTOR to control food intake, our data show that the activation of these enzymes occurs in the same specific neuronal subtypes. CONCLUSIONS: These findings provide support for the hypothesis that AMPK and mTOR interact in the hypothalamus to regulate feeding during HPD in a leucine-dependent manner.
Eduardo R Ropelle; José R Pauli; Maria Fernanda A Fernandes; Silvana A Rocco; Rodrigo M Marin; Joseane Morari; Kellen K Souza; Marília M Dias; Maria C Gomes-Marcondes; José A R Gontijo; Kleber G Franchini; Lício A Velloso; Mario J A Saad; José B C Carvalheira
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-12-05
Journal Detail:
Title:  Diabetes     Volume:  57     ISSN:  1939-327X     ISO Abbreviation:  Diabetes     Publication Date:  2008 Mar 
Date Detail:
Created Date:  2008-02-28     Completed Date:  2008-03-21     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0372763     Medline TA:  Diabetes     Country:  United States    
Other Details:
Languages:  eng     Pagination:  594-605     Citation Subset:  AIM; IM    
Department of Internal Medicine, State University of Campinas (UNICAMP), 13083-970, Campinas, São Paulo, Brazil.
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MeSH Terms
AMP-Activated Protein Kinases
Body Composition
Dietary Proteins / pharmacology*
Dietary Supplements
Eating / drug effects
Leucine / pharmacology
Mice, Inbred NOD
Mice, Obese
Multienzyme Complexes / metabolism*
Neurons / enzymology*
Protein Kinases / genetics,  metabolism*
Protein-Serine-Threonine Kinases / metabolism*
Rats, Wistar
Time Factors
Weight Loss / drug effects*
Reg. No./Substance:
0/Dietary Proteins; 0/Multienzyme Complexes; 61-90-5/Leucine; EC 2.7.-/Protein Kinases; EC 2.7.1.-/mTOR protein; EC Protein Kinases; EC Kinases

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