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An identity crisis of satiety neurons: how prolonged metabolic stress can reprogram the hypothalamus

Principal Investigator:
  • Alexandre Fisette, Université du Québec à Trois-Rivières
  • Azrieli Foundation

Project Overview

The prevalence of obesity has reached pandemic levels and represents a massive societal and economic burden. Findings of the last decades on how the brain controls what is known as energy balance, or the “Energy In, Energy out”, have pushed scientists to consider obesity as a disease of the nervous system. Indeed, prolonged obesity is associated with a durable change in the “defended body weight”, which ultimately impairs the capacity to lose weight and maintain that loss over time. One of the main brain networks in charge of maintaining body weight stable is known as the “melanocortin system”, which consists of two different groups of neurons, the satiety-inducing Pomc neurons and the appetite-inducing Agrp neurons. Prolonged obesity is especially detrimental for the satiety-inducing neurons, and studies in mice have shown that, in this context, between 25-50% of them disappear. While it was supposed that these satiety neurons were dying, preliminary results from my laboratory indicate that these neurons are very much alive, and are rather undergoing significant changes in their identity, losing their capacity to induce satiety. My laboratory aims at understanding how such changes of identity can occur, and what are the consequences of these changes on body weight maintenance. To do so, we will use mouse models of obesity and neuronal cell cultures.