Mediobasal hypothalamic leucine sensing regulates food intake through activation of a hypothalamus-brainstem circuit

Clémence Blouet, Young Hwan Jo, Xiaosong Li, Gary J. Schwartz

Research output: Contribution to journalArticle

143 Scopus citations

Abstract

In response to nutrient stimuli, the mediobasal hypothalamus (MBH) drives multiple neuroendocrine and behavioral mechanisms to regulate energy balance. While central leucine reduces food intake and body weight, the specific neuroanatomical sites of leucine sensing, downstream neural substrates, and neurochemical effectors involved in this regulation remain largely unknown. Here we demonstrate that MBH leucine engages a neural energy regulatory circuit by stimulating POMC (proopiomelanocortin) neurons of the MBH, oxytocin neurons of the paraventricular hypothalamus, and neurons within the brainstem nucleus of the solitary tract to acutely suppress food intake by reducing meal size. We identify central p70 S6 kinase and Erk1/2 pathways as intracellular effectors required for this response. Activation of endogenous leucine intracellular metabolism produced longer-term reductions in meal number. Our data identify a novel, specific hypothalamus-brainstem circuit that links amino acid availability and nutrient sensing to the control of food intake.

Original languageEnglish (US)
Pages (from-to)8302-8311
Number of pages10
JournalJournal of Neuroscience
Volume29
Issue number26
DOIs
StatePublished - Jul 1 2009

ASJC Scopus subject areas

  • Neuroscience(all)

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