Feeding behavior is exquisitely regulated by homeostatic and hedonic neural substrates that integrate energy demand as well as the reinforcing and rewarding aspects of food. Understanding the net contribution of homeostatic and reward-driven feeding has become critical due to the ubiquitous source of energy-dense foods and the consequent obesity epidemic. Hypothalamic, agouti-related protein-secreting neurons (AgRP neurons) represent primary orexigenic drives of homeostatic feeding. Using a models of neuronal inhibition or ablation we demonstrate that the feeding response to a fast, ghrelin or serotonin receptor agonist relies on AgRP neurons; however, when palatable food is provided, AgRP neurons are dispensable for an appropriate feeding response. In addition, AgRP-ablated mice present exacerbated stress-induced anorexia and palatable food intakea hallmark of comfort feeding. These results demonstrate that hedonic circuitry can solely operate feeding and override the homeostatic circuitry especially in conditions where positive response to energy demands is chronically defective.
10 - 12 Sep 2016
European Society for Paediatric Endocrinology