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Hypothalamic AgRP‐neurons control peripheral substrate utilization and nutrient partitioning
Author(s) -
JolyAmado Aurélie,
Denis Raphaël G P,
Castel Julien,
Lacombe Amélie,
Cansell Céline,
Rouch Claude,
Kassis Nadim,
Dairou Julien,
Cani Patrice D,
VenturaClapier Renée,
Prola Alexandre,
Flamment Melissa,
Foufelle Fabienne,
Magnan Christophe,
Luquet Serge
Publication year - 2012
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2012.250
Subject(s) - biology , endocrinology , nutrient , medicine , dyslipidemia , hypothalamus , efferent , obesity , neuroscience , ecology , afferent
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.