Mediobasal hypothalamic leucine sensing regulates food intake through activation of a hypothalamus-brainstem circuit. The Journal of neuroscience : the official journal of the Society for Neuroscience [J Neurosci] Journal article

Title	Mediobasal hypothalamic leucine sensing regulates food intake through activation of a hypothalamus-brainstem circuit.
Author(s)	Blouet C, Jo YH, Li X, Schwartz GJ
Institution	Department of Medicine, Albert Einstein College of Medicine of Yeshiva University, Bronx, New York 10461, USA.
Source	J Neurosci 2009 Jul 1; 29(26):8302-11.
MeSH	Animals Anorexia Body Weight Bone Morphogenetic Protein Receptors, Type I Brain Stem Butadienes Dose-Response Relationship, Drug Drug Administration Schedule Eating Enzyme Inhibitors Feeding Behavior Green Fluorescent Proteins Hypothalamus Injections, Intraventricular Keto Acids Leucine Male Melanocortins Melanocyte-Stimulating Hormones Mice Mice, Inbred C57BL Mice, Transgenic Neural Pathways Neurons Nitriles Oxytocin Pro-Opiomelanocortin Proto-Oncogene Proteins c-fos Rats Rats, Sprague-Dawley Signal Transduction Threonine Time Factors Tyrosine Vasotocin
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.
Language	eng
Pub Type(s)	In Vitro Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't
PubMed ID	19571121

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