Modulation of hypothalamic S6K1 and S6K2 alters feeding behavior and systemic glucose metabolism

in Journal of Endocrinology
Authors:
Mariana Rosolen Tavares Multidisciplinary Laboratory of Food and Health (LABMAS), School of Applied Sciences (FCA), University of Campinas (UNICAMP), Limeira, São Paulo, Brazil
Laboratory of Metabolic Disorders (LABDIME), School of Applied Sciences (FCA), University of Campinas (UNICAMP), Limeira, São Paulo, Brazil

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Simone Ferreira Lemes Laboratory of Metabolic Disorders (LABDIME), School of Applied Sciences (FCA), University of Campinas (UNICAMP), Limeira, São Paulo, Brazil

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Thais de Fante Laboratory of Metabolic Disorders (LABDIME), School of Applied Sciences (FCA), University of Campinas (UNICAMP), Limeira, São Paulo, Brazil

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Cristina Saenz de Miera Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan, USA

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Isadora Carolina Betim Pavan Multidisciplinary Laboratory of Food and Health (LABMAS), School of Applied Sciences (FCA), University of Campinas (UNICAMP), Limeira, São Paulo, Brazil
Laboratory of Metabolic Disorders (LABDIME), School of Applied Sciences (FCA), University of Campinas (UNICAMP), Limeira, São Paulo, Brazil

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Rosangela Maria Neves Bezerra Multidisciplinary Laboratory of Food and Health (LABMAS), School of Applied Sciences (FCA), University of Campinas (UNICAMP), Limeira, São Paulo, Brazil

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Patricia Oliveira Prada Laboratory of Molecular Research in Obesity (LABIMO), School of Applied Sciences (FCA), University of Campinas (UNICAMP), Limeira, São Paulo, Brazil

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Marcio Alberto Torsoni Laboratory of Metabolic Disorders (LABDIME), School of Applied Sciences (FCA), University of Campinas (UNICAMP), Limeira, São Paulo, Brazil

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Carol Fuzeti Elias Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan, USA

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Fernando Moreira Simabuco Multidisciplinary Laboratory of Food and Health (LABMAS), School of Applied Sciences (FCA), University of Campinas (UNICAMP), Limeira, São Paulo, Brazil
Laboratory of Metabolic Disorders (LABDIME), School of Applied Sciences (FCA), University of Campinas (UNICAMP), Limeira, São Paulo, Brazil

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Correspondence should be addressed to F M Simabuco: simabuco@gmail.com
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The mTOR/S6Ks signaling is one of the intracellular pathways important for metabolic control, acting both peripherally and centrally. In the hypothalamus, mTOR/S6Ks axis mediates the action of leptin and insulin and can modulate the expression of neuropeptides. We analyzed the role of different S6Ks isoforms in the hypothalamic regulation of metabolism. We observed decreased food intake and decreased expression of agouti-related peptide (AgRP) following intracerebroventricular (icv) injections of adenoviral-mediated overexpression of three different S6Ks isoforms. Moreover, mice overexpressing p70-S6K1 in undefined periventricular hypothalamic neurons presented changes in glucose metabolism, as an increase in gluconeogenesis. To further evaluate the hypothalamic role of a less-studied S6K isoform, p54-S6K2, we used a Cre-LoxP approach to specifically overexpress it in AgRP neurons. Our findings demonstrate the potential participation of S6K2 in AgRP neurons regulating feeding behavior.

 

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