Hypothalamic S1P/S1PR1 axis controls energy homeostasis

Vagner R. R. Silva, Thayana O. Micheletti, Gustavo D. Pimentel, Carlos K. Katashima, Luciene Lenhare, Joseane Morari, Maria Carolina S. Mendes, Daniela S. Razolli, Guilherme Z. Rocha, Claudio T. de Souza, Dongryeol Ryu, Patrícia O. Prada, Lício A. Velloso, José B. C. Carvalheira, José Rodrigo Pauli, Dennys E. Cintra and Eduardo R. Ropelle ()
Additional contact information
Vagner R. R. Silva: Laboratory of Molecular Biology of Exercise (LaBMEx). School of Applied Science, University of Campinas (UNICAMP), Rua Pedro Zaccarias, 1300, CEP 13484-350 Limeira, São Paulo, Brazil
Thayana O. Micheletti: Faculty of Medical Sciences, University of Campinas (UNICAMP)
Gustavo D. Pimentel: Faculty of Medical Sciences, University of Campinas (UNICAMP)
Carlos K. Katashima: Faculty of Medical Sciences, University of Campinas (UNICAMP)
Luciene Lenhare: Faculty of Medical Sciences, University of Campinas (UNICAMP)
Joseane Morari: Laboratory of Cell Signalling, Faculty of Medical Sciences, University of Campinas (UNICAMP)
Maria Carolina S. Mendes: Faculty of Medical Sciences, University of Campinas (UNICAMP)
Daniela S. Razolli: Laboratory of Cell Signalling, Faculty of Medical Sciences, University of Campinas (UNICAMP)
Guilherme Z. Rocha: Faculty of Medical Sciences, University of Campinas (UNICAMP)
Claudio T. de Souza: Laboratory of Exercise Biochemistry and Physiology, Health Sciences Unit, University of Southern Santa Catarina
Dongryeol Ryu: Laboratory of Integrative and Systems Physiology, School of Life Sciences, École Polytechnique Fédérale de Lausanne
Patrícia O. Prada: Faculty of Medical Sciences, University of Campinas (UNICAMP)
Lício A. Velloso: Laboratory of Cell Signalling, Faculty of Medical Sciences, University of Campinas (UNICAMP)
José B. C. Carvalheira: Faculty of Medical Sciences, University of Campinas (UNICAMP)
José Rodrigo Pauli: Laboratory of Molecular Biology of Exercise (LaBMEx). School of Applied Science, University of Campinas (UNICAMP), Rua Pedro Zaccarias, 1300, CEP 13484-350 Limeira, São Paulo, Brazil
Dennys E. Cintra: Laboratory of Molecular Biology of Exercise (LaBMEx). School of Applied Science, University of Campinas (UNICAMP), Rua Pedro Zaccarias, 1300, CEP 13484-350 Limeira, São Paulo, Brazil
Eduardo R. Ropelle: Laboratory of Molecular Biology of Exercise (LaBMEx). School of Applied Science, University of Campinas (UNICAMP), Rua Pedro Zaccarias, 1300, CEP 13484-350 Limeira, São Paulo, Brazil

Nature Communications, 2014, vol. 5, issue 1, 1-15

Abstract: Abstract Sphingosine 1-phosphate receptor 1 (S1PR1) is a G-protein-coupled receptor for sphingosine-1-phosphate (S1P) that has a role in many physiological and pathophysiological processes. Here we show that the S1P/S1PR1 signalling pathway in hypothalamic neurons regulates energy homeostasis in rodents. We demonstrate that S1PR1 protein is highly enriched in hypothalamic POMC neurons of rats. Intracerebroventricular injections of the bioactive lipid, S1P, reduce food consumption and increase rat energy expenditure through persistent activation of STAT3 and the melanocortin system. Similarly, the selective disruption of hypothalamic S1PR1 increases food intake and reduces the respiratory exchange ratio. We further show that STAT3 controls S1PR1 expression in neurons via a positive feedback mechanism. Interestingly, several models of obesity and cancer anorexia display an imbalance of hypothalamic S1P/S1PR1/STAT3 axis, whereas pharmacological intervention ameliorates these phenotypes. Taken together, our data demonstrate that the neuronal S1P/S1PR1/STAT3 signalling axis plays a critical role in the control of energy homeostasis in rats.

Date: 2014
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DOI: 10.1038/ncomms5859

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