The arcuate nucleus of the hypothalamus contains at least two populations of neurons that continuously monitor signals reflecting energy status and promote the appropriate behavioral and metabolic responses to changes in energy demand. Activation of neurons making pro-opiomelanocortin (POMC) decreases food intake and increases energy expenditure through activation of G protein-coupled melanocortin receptors via the release of α-melanocyte-stimulating hormone. Until recently, the prevailing idea was that the neighboring neurons [agouti-related protein (AgRP) neurons] co-expressing the orexigenic neuropeptides, AgRP, and neuropeptide Y increase feeding by opposing the anorexigenic actions of the POMC neurons. However, it has now been demonstrated that only AgRP neurons activation - not POMC neurons inhibition - is necessary and sufficient to promote feeding. Projections of AgRP-expressing axons innervate mesolimbic, midbrain, and pontine structures where they regulate feeding and feeding-independent functions such as reward or peripheral nutrient partitioning. AgRP neurons also make gamma aminobutyric acid , which is now thought to mediate many of critical functions of these neurons in a melanocortin-independent manner and on a timescale compatible with neuromodulation.
This work was supported by young investigator ATIP grant from the CNRS, a research fellowship from and a grant by the “Agence Nationale de la Recherche” ANR-09-BLAN-0267-02.
Céline Cansell received a PhD fellowship from the Centre National de la Recherche Scientifique (CNRS) and a research grant from the Société Francophone du Diabète-Roche (SFD). Aurélie Joly Amado received a National Merit Scholarship from the French Department of National Education and Research and a research grant from the SFNEP-ANTADIR. Raphaël G. P. Denis received a research fellowship from the Region Île-de-France. We would like to express our gratitude to Richard D. Palmiter and Diane Durnam for fruitful comments on the manuscript and for editing.
- neuropeptide Y
- agouti-related protein
- feeding behavior