Contrôle hypothalamique de la balance énergétique par les lipides et physiopathologie de l'obésité

 

Thierry Alquier

Centre hospitalier de l'Université de Montréal [CHUM]

 

Domaine : nutrition et métabolisme

Programme Chercheurs-boursiers - Senior

Concours 2018-2019

Obesity affects nearly 14 million Canadians and is a major risk factor for diabetes. Our understanding of how and why obesity occurs is incomplete but the dramatic increase in obesity is partly due to the increased intake of food that has a high-fat content.

The hypothalamus is a brain region that plays a critical role in controlling body weight by regulating food intake and the amount of calories burned. The activity of hypothalamic neurons is strongly regulated by hormones and nutrients circulating in the blood. In turn, these neurons activate appropriate physiological responses to maintain a proper body weight.

However, how and which cells in the brain sense changes in circulating fatty acids to regulate blood glucose and energy balance is unknown. We, as well as others, suggest that hypothalamic glial cells, a cell-type surrounding neurons, can regulate neuronal activity via cell-to-cell communication and energy balance. Our preliminary results suggest that fatty acids are detected by hypothalamic glial cells via different signaling mechanisms and that disruption of these mechanisms leads to obesity.

The overall goal of our research is to determine the role and the mechanisms by which fatty acids are detected by glial cells to regulate the activity of hypothalamic neurons and energy balance. We propose to explore our goals using a combination of pharmacological and genetic strategies to precisely modulate fatty acid detection and signaling in rodents.

With growing health concerns regarding obesity and diabetes, it is critical to understand the mechanisms underlying these diseases. We believe the novel contribution of glial-derived signals in the hypothalamus is key to controlling energy balance and the underlying cause to these pathologies. Identifying causative and druggable targets for obesity and diabetes that could be challenged with prospective therapies remains an unmet clinical need.