Hypothalamic S1P/S1PR1 axis controls energy homeostasis

Author(s):Show less -

Silva, Vagner R. R. ^[1] ; Micheletti, Thayana O. ^[2] ; Pimentel, Gustavo D. ^[2] ; Katashima, Carlos K. ^[2] ; Lenhare, Luciene ^[2] ; Morari, Joseane ^[3] ; Mendes, Maria Carolina S. ^[2] ; Razolli, Daniela S. ^[3] ; Rocha, Guilherme Z. ^[2] ; de Souza, Claudio T. ^[4] ; Ryu, Dongryeol ^[5] ; Prada, Patricia O. ^[2] ; Velloso, Licio A. ^[3] ; Carvalheira, Jose B. C. ^[2] ; Pauli, Jose Rodrigo ^[1] ; Cintra, Dennys E. ^{[2, 1, 3]} ; Ropelle, Eduardo R. ^{[2, 1]}

Affiliation

^[1] Univ Estadual Campinas, Sch Appl Sci, Lab Mol Biol Exercise LaBMEx, BR-13484350 Limeira, SP - Brazil

^[2] Univ Estadual Campinas, Fac Med Sci, Dept Internal Med, BR-13083887 Campinas, SP - Brazil

^[3] Univ Estadual Campinas, Fac Med Sci, Lab Cell Signalling, BR-13083887 Campinas, SP - Brazil

^[4] Univ Southern Santa Catarina, Lab Exercise Biochem & Physiol, Hlth Sci Unit, BR-88806000 Criciuma, SC - Brazil

^[5] Ecole Polytech Fed Lausanne, Sch Life Sci, Lab Integrat & Syst Physiol, CH-1015 Lausanne - Switzerland

• Document type: Journal article
• Source: NATURE COMMUNICATIONS; v. 5, SEP 2014.
• Web of Science Citations: 22

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. (AU)

• FAPESP's process: 11/09656-0 - Characterization of hypothalamic S1PR1 in the control of food intake in rodents
• Grantee: Eduardo Rochete Ropelle
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 11/13828-1 - Effects of physical exercise on leptin signaling in the hypothalamus of rats: The role of neuronal S1PR1.
• Grantee: Vagner Ramon Rodrigues Silva
• Support Opportunities: Scholarships in Brazil - Master