Inactivation of Socs3 in the hypothalamus enhances the hindbrain response to endogenous satiety signals via oxytocin signaling
2012
Matarazzo, Valéry | Schaller, Fabienne | Nédélec, Emmanuelle | Benani, Alexandre | Pénicaud, Luc | Muscatelli, Françoise | Moyse, Emmanuel | Bauer, Sylvian | Centre de recherche en neurobiologie - neurophysiologie de Marseille (CRN2M) ; Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) | Institut de Neurobiologie de la Méditerranée [Aix-Marseille Université] (INMED - INSERM U901) ; Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM) | Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA) ; Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS) | Physiologie de la reproduction et des comportements [Nouzilly] (PRC) ; Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur] (IFCE)-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS) | Centre National de la Recherche Scientifique, Institut National de la Sante et de la Recherche Medicale, Institut National de la Recherche Agronomique, Universite Aix-Marseille, Societe Francaise de Nutrition
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Show more [+] Less [-]English. Leptin is an adipocyte-derived hormone that controls energy balance by acting primarily in the CNS, but its action is lost in common forms of obesity due to central leptin resistance. One potential mechanism for such leptin resistance is an increased hypothalamic expression of Suppressor of cytokine signaling 3 (Socs3), a feedback inhibitor of the Jak-Stat pathway that prevents Stat3 activation. Ample studies have confirmed the important role of Socs3 in leptin resistance and obesity. However, the degree to which Socs3 participates in the regulation of energy homeostasis in nonobese conditions remains largely undetermined. In this study, using adult mice maintained under standard diet, we demonstrate that Socs3 deficiency in the mediobasal hypothalamus (MBH) reduces food intake, protects against body weight gain, and limits adiposity, suggesting that Socs3 is necessary for normal body weight maintenance. Mechanistically, MBH Socs3-deficient mice display increased hindbrain sensitivity to endogenous, meal-related satiety signals, mediated by oxytocin signaling. Thus, oxytocin signaling likely mediates the effect of hypothalamic leptin on satiety circuits of the caudal brainstem. This provides an anatomical substrate for the effect of leptin on meal size, and more generally, a mechanism for how the brain controls short-term food intake as a function of the energetic stores available in the organism to maintain energy homeostasis. Any dysfunction in this pathway could potentially lead to overeating and obesity.
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