Project Overview

The central nervous system controls numerous processes, including appetite and body weight regulation. Given the alarming rise in global obesity, understanding how the CNS controls appetite is crucial. Among the cell types involved, neurons expressing the gene “Pro-opiomelanocortin” (POMC) are particularly important. Loss of POMC neurons or the POMC gene leads to obesity in humans and rodents. Despite their known role, acutely activating POMC neurons does not reduce food intake, raising questions about their short-term functions.

We hypothesize that this discrepancy arises because POMC neurons have subpopulations that are either excitatory or inhibitory; thus, activating all POMC neurons cancels out the effects. We propose developing a toolkit to study POMC subpopulations to define their roles in regulating energy balance. We will conduct studies to acutely activate either excitatory or inhibitory POMC subpopulations and quantify changes in food intake. Additionally, we will permanently silence both subpopulations and track longterm changes in body weight. Finally, we will define the neuroanatomical connections of both excitatory and inhibitory POMC neurons.

Together, we expect our studies to demonstrate that excitatory POMC neurons are the most critical for regulating short-term food intake and long-term body weight. We do not expect this to be due to different anatomy of the cells, but if we find this is the case, it would be a novel and exciting finding. Our research will answer longstanding questions about the roles of POMC neurons in energy balance. Future directions will focus on understanding how obesity impacts each subpopulation and exploring ways to target POMC subpopulations to treat obesity and its comorbidities.

Principal Investigator

Paul Sabatini , L’institut de recherche du Centre universitaire de santé McGill / Research Institute of the McGill University Health Centre