Hypothalamic S1P/S1PR1 axis controls energy homeostasis in Middle-Aged Rodents: the reversal effects of physical exercise

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Rodrigues Silva, Vagner Ramon ; Katashima, Carlos Kiyoshi ; Bueno Silva, Carla G. ; Lenhare, Luciene ; Micheletti, Thayana Oliveira ; Camargo, Rafael Ludemann ; Ghezzi, Ana Carolina ; Camargo, Juliana Alves ; Assis, Alexandre Moura ; Tobar, Natalia ; Morari, Joseane ; Razolli, Daniela S. ; Moura, Leandro Pereira ; Pauli, Jose Rodrigo ; Cintra, Dennys Esper ; Velloso, Licio Augusto ; Saad, Mario J. A. ; Ropelle, Eduardo Rochete

• Tipo de documento: Artigo Científico
• Fonte: AGING-US; v. 9, n. 1, p. 156-169, JAN 2017.
• Citações Web of Science: 5

Resumo

Recently, we demonstrated that the hypothalamic S1PR1/STAT3 axis plays a critical role in the control of food consumption and energy expenditure in rodents. Here, we found that reduction of hypothalamic S1PR1 expression occurs in an age-dependent manner, and was associated with defective thermogenic signaling and weight gain. To address the physiological relevance of these findings, we investigated the effects of chronic and acute exercise on the hypothalamic S1PR1/STAT3 axis. Chronic exercise increased S1PR1 expression and STAT3 phosphorylation in the hypothalamus, restoring the anorexigenic and thermogenic signals in middle-aged mice. Acutely, exercise increased sphingosine-1-phosphate (S1P) levels in the cerebrospinal fluid (CSF) of young rats, whereas the administration of CSF from exercised young rats into the hypothalamus of middle-aged rats at rest was sufficient to reduce the food intake. Finally, the intracerebroventricular (ICV) administration of S1PR1 activators, including the bioactive lipid molecule S1P, and pharmacological S1PR1 activator, SEW2871, induced a potent STAT3 phosphorylation and anorexigenic response in middle-aged rats. Overall, these results suggest that hypothalamic S1PR1 is important for the maintenance of energy balance and provide new insights into the mechanism by which exercise controls the anorexigenic and thermogenic signals in the central nervous system during the aging process. (AU)

• Processo FAPESP: 11/09656-0 - Caracterização da proteína S1PR1 hipotalâmica no controle da ingestão alimentar em roedores
• Beneficiário: Eduardo Rochete Ropelle
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 11/13828-1 - Efeitos do exercício físico sobre a sinalização da leptina no hipotálamo de ratos: O papel da S1PR1 neuronal.
• Beneficiário: Vagner Ramon Rodrigues Silva
• Modalidade de apoio: Bolsas no Brasil - Mestrado