Journal
EMBO JOURNAL
Volume 31, Issue 22, Pages 4276-4288Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/emboj.2012.250
Keywords
diabetes; metabolism; obesity
Categories
Funding
- CNRS
- Region Ile-de-France
- University Paris Diderot-Paris 7
- Societe Francophone du Diabete-Lilly
- Agence Nationale de la Recherche [ANR-09-BLAN-0267-02]
- French Department of National Education and Research
- SFNEP-ANTADIR
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Obesity-related diseases such as diabetes and dyslipidemia result from metabolic alterations including the defective conversion, storage and utilization of nutrients, but the central mechanisms that regulate this process of nutrient partitioning remain elusive. As positive regulators of feeding behaviour, agouti-related protein (AgRP) producing neurons are indispensible for the hypothalamic integration of energy balance. Here, we demonstrate a role for AgRP-neurons in the control of nutrient partitioning. We report that ablation of AgRP-neurons leads to a change in autonomic output onto liver, muscle and pancreas affecting the relative balance between lipids and carbohydrates metabolism. As a consequence, mice lacking AgRP-neurons become obese and hyperinsulinemic on regular chow but display reduced body weight gain and paradoxical improvement in glucose tolerance on high-fat diet. These results provide a direct demonstration of a role for AgRP-neurons in the coordination of efferent organ activity and nutrient partitioning, providing a mechanistic link between obesity and obesity-related disorders. The EMBO Journal (2012) 31, 4276-4288. doi:10.1038/emboj.2012.250; Published online 18 September 2012
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