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A CENTRAL ROLE FOR NEURONAL AMPK and mTOR IN HIGH PROTEIN DIET-INDUCED WEIGHT LOSS

¹Department of Internal Medicine, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas, SP, Brazil
²Department of Physiology and Biophysics of State University of Campinas (UNICAMP), Campinas, SP, Brazil

Objective: High protein diet (HPD) is known to promote the reduction of body fat, but the mechanisms underlying this change are unclear. AMPK and mTOR function as majors regulators of cellular metabolism that responds 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 HPD.

Research design and Methods: Western blotting, confocal microscopy, chromatography, light microscopy and RT-PCR assays were combined to explore the anorexigenic effects of HPD.

Results: 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 HPD. Leucine and HPD decreases AMPK and increases mTOR activity in the hypothalamus, leading to inhibition of NPY and stimulation of POMC 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 sub types.

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.

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