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Type: Artigo de periódico
Title: A Central Role For Neuronal Amp-activated Protein Kinase (ampk) And Mammalian Target Of Rapamycin (mtor) In High-protein Diet-induced Weight Loss.
Author: Ropelle, Eduardo R
Pauli, José R
Fernandes, Maria Fernanda A
Rocco, Silvana A
Marin, Rodrigo M
Morari, Joseane
Souza, Kellen K
Dias, Marília M
Gomes-Marcondes, Maria C
Gontijo, José A R
Franchini, Kleber G
Velloso, Lício A
Saad, Mario J A
Carvalheira, José B C
Abstract: 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. Western blotting, confocal microscopy, chromatography, light microscopy, and RT-PCR assays were combined to explore the anorexigenic effects of an HPD. 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. 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.
Subject: Amp-activated Protein Kinases
Body Composition
Dietary Proteins
Dietary Supplements
Mice, Inbred Nod
Mice, Obese
Multienzyme Complexes
Protein Kinases
Protein-serine-threonine Kinases
Rats, Wistar
Tor Serine-threonine Kinases
Time Factors
Weight Loss
Citation: Diabetes. v. 57, n. 3, p. 594-605, 2008-Mar.
Rights: fechado
Identifier DOI: 10.2337/db07-0573
Date Issue: 2008
Appears in Collections:Unicamp - Artigos e Outros Documentos

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