Skip to Content
Merck
  • Hypothalamic AgRP-neurons control peripheral substrate utilization and nutrient partitioning.

Hypothalamic AgRP-neurons control peripheral substrate utilization and nutrient partitioning.

The EMBO journal (2012-09-20)
Aurélie Joly-Amado, Raphaël G P Denis, Julien Castel, Amélie Lacombe, Céline Cansell, Claude Rouch, Nadim Kassis, Julien Dairou, Patrice D Cani, Renée Ventura-Clapier, Alexandre Prola, Melissa Flamment, Fabienne Foufelle, Christophe Magnan, Serge Luquet
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Bretazenil, ≥96% (HPLC), solid
Pricing and availability is not currently available.