Project: Impact of the nature of lipids on neuroinflammation and glial reactivity, associated with the development of obesity.

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Keywords: Lipids, Neuroinflammation, Glial reactivity, Nutritional obesity

This project aims to understand the mechanisms involved in the brain's inflammatory response induced by different types of dietary fats (animal and vegetable). Obesity affects nearly 151 million people worldwide, including 41 million children. Studies conducted on animal models and humans show that peripheral organs, affected by the excess fat in the Western diet, communicate with the hypothalamic neural centers involved in controlling eating behavior, thereby altering its function. Obesity and metabolic syndromes correspond to a state of chronic systemic inflammation that leads to dysregulation of eating behavior. The changes induced by a high-fat diet are complex and still poorly understood. They may primarily involve glial cells (astrocytes and/or microglia) that form the blood-brain barrier and are responsible for the inflammatory response in the brain.

We hypothesize that The activation of these cells would be important from the first hours after the meal. We work with a mouse model fed different diets rich in fats of different origins (animal or vegetable) and types (omega-6/omega-3). We characterize the impact of these diets on the development of obesity, associated neuroinflammation, and glial reactivity.

Furthermore, we propose to develop a image processing/analysis procedure This allows for the automatic measurement of astrocytic extension size and microglial morphological changes, enabling the determination of these cells' activation (collaboration with Eric Debreuve/Morphème Team, I3S). We will attempt to determine whether inhibiting this activation could prevent obesity, thereby offering an innovative therapeutic approach for its treatment.

The work was also supported by the NUTRINEURO project funded by the Université Côte d'Azur (UCA-IDEX, Academy 3 "Space, environment, risks and resilience") over the period 2019-2021, for an amount of €35,000, as part of a project coordinated by the team.

They also benefited from the support of the French National Research Agency (ANR) as part of the 2021 generic call for projects (MicroFlamEAT project), focusing on the role of the postprandial microglial inflammatory response in the cerebral control of appetite, with €90,000 in funding awarded to the team as a partner.

Related publications:

Cansell C et al. (2020) Glia 69:42-60.

Nuzzaci D et al. (2020) Cell Rep. 30:3067-3078.