Calcitonin gene-related peptide-induced phosphorylation of STAT3 in arcuate neurons is a link in the metabolic benefits of portal glucose - Archive ouverte HAL Access content directly
Journal Articles Neuroendocrinology Year : 2020

Calcitonin gene-related peptide-induced phosphorylation of STAT3 in arcuate neurons is a link in the metabolic benefits of portal glucose

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Abstract

Introduction: Intestinal gluconeogenesis exerts metabolic benefits in energy homeostasis via the neural sensing of portal glucose. Objective: The aim of this work was to determine central mechanisms involved in the effects of intestinal gluconeogenesis (IGN) on the control of energy homeostasis. Methods: We investigated the effects of glucose infusion into the portal vein, at a rate that mimics IGN, in conscious wild-type, leptin-deficient ob/ob and CGRP-/- mice. Results: We report that portal glucose infusion decreases food intake and plasma glucose and induces in the hypothalamic arcuate nucleus (ARC) the phosphorylation of STAT3, the classic intracellular messenger of leptin signaling. This notably takes place in POMC-expressing neurons. STAT3-phosphorylation does not require leptin, since portal glucose effects are observed in leptin-deficient (ob/ob) mice. We hypothesized that the portal glucose effects could require calcitonin gene-related peptide (CGRP), a neuromediator previously suggested to suppress hunger. In line with this hypothesis, neither the metabolic benefits nor the phosphorylation of STAT3 in the ARC take place upon portal glucose infusion in CGRP-deficient mice. Moreover, intracerebroventricular injection of CGRP activates hypothalamic phosphorylation of STAT3 in mice, and CGRP does the same in hypothalamic cells. Finally, no metabolic benefit of dietary fibers (known to depend on the induction of IGN), takes place in CGRP deficient mice. Conclusions: CGRP-induced phosphorylation of STAT3 in the ARC is part of the neural chain determining the hunger-modulating and glucose-lowering effects of IGN/portal glucose. Conclusions: CGRP-induced phosphorylation of STAT3 in the ARC is part of the neural chain determining the hunger-modulating and glucose-lowering effects of IGN/portal glucose.
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inserm-02998340 , version 1 (10-11-2020)

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Maud Soty, Justine Vily-Petit, Ashley Castellanos-Jankiewicz, Omar Guzman-Quevedo, Margaux Raffin, et al.. Calcitonin gene-related peptide-induced phosphorylation of STAT3 in arcuate neurons is a link in the metabolic benefits of portal glucose. Neuroendocrinology, 2020, Online ahead of print. ⟨10.1159/000509230⟩. ⟨inserm-02998340⟩
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