NUTRINEURO

The consumption of "Western" diets with high sugar and fat content combined with a decrease in the consumption of vegetables, fiber, cereals and bread and a generally low level of physical activity, has led to an increased prevalence of obesity in Western countries (Europe, USA, etc.). These Western obesogenic diets are dangerous to health because they have excessive amounts of saturated and polyunsaturated fatty acids (PUFAs), such as the deleterious pro-inflammatory omega-6 type (Ω-6). The Ω-6 fatty acid can indeed dramatically alter the integrity of the coronary artery walls, while the lack of omega-3 (Ω-3), an anti-inflammatory fatty acid, can increase the deleterious action of Ω-6. The past 40 years have been marked by a drastic increase in the Ω-6/Ω-3 ratios in the diet of the French and Western populations which now stands at around 8; an ideal ratio would be less than 5. The failure to respect a certain Ω-6/Ω-3 balance could predispose people to inflammatory developments which generally initiate a variety of diseases including obesity and associated problems (cardiovascular disease, stroke, etc.).

The purpose of this project is to characterize the impact of different lipid categories on obesity development and the associated occurrence of inflammation. For 4, 8 and 16 weeks, we fed mice with different hyperlipidic diets (enriched in butter, rapeseed, soybean/corn, or sunflower) containing a range of Ω-6/Ω-3 ratios (2.3-17.5), and compared this to a standard diet. From the analyses of inflammatory profiles, we could show that it was not only the amount but also the nature of the lipids contained in the hyperlipidic diets that affected the inflammatory molecule production in both peripheral circulation and the hypothalamus (brain region involved in feeding behavior regulation). Using an innovative pharmacogenetics approach (DREADD technology) made to specifically inhibit the two major brain cells involved in feeding behavior (glial cells, and more specifically astrocytes and microglia), we also revealed the implication of the hypothalamic activation of those cells in the development of obesity. However, this brain cell activation seems to be reversible, which suggests that resilient strategies will be possible.