Affiliation:
1. Faculty of Pharmacy Université Laval Quebec City Quebec Canada
2. Quebec Heart and Lung Institute Quebec City Quebec Canada
3. Montreal Diabetes Research Center Montreal Quebec Canada
Abstract
AbstractThe discovery of leptin in 1994 was an “eureka moment” in the field of neurometabolism that provided new opportunities to better understand the central control of energy balance and glucose metabolism. Rapidly, a prevalent model in the field emerged that pro‐opiomelanocortin (POMC) neurons were key in promoting leptin's anorexigenic effects and that the arcuate nucleus of the hypothalamus (ARC) was a key region for the regulation of energy homeostasis. While this model inspired many important discoveries, a growing body of literature indicates that this model is now outdated. In this review, we re‐evaluate the hypothalamic leptin–melanocortin model in light of recent advances that directly tackle previous assumptions, with a particular focus on the ARC. We discuss how segregated and heterogeneous these neurons are, and examine how the development of modern approaches allowing spatiotemporal, intersectional, and chemogenetic manipulations of melanocortin neurons has allowed a better definition of the complexity of the leptin–melanocortin system. We review the importance of leptin in regulating glucose homeostasis, but not food intake, through direct actions on ARC POMC neurons. We further highlight how non‐POMC, GABAergic neurons mediate leptin's direct effects on energy balance and influence POMC neurons.image
Funder
Canada Research Chairs
Canadian Institutes of Health Research
Natural Sciences and Engineering Research Council of Canada
Sleep Research Society Foundation
Canada First Research Excellence Fund
Fonds de Recherche du Québec - Santé
Subject
Cellular and Molecular Neuroscience,Biochemistry
Cited by
3 articles.
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