Polynut : impact of polyphenol consumption on the coping mechanisms induced by overeating in humans ; Polynut : impact de la consommation de polyphénols sur les mécanismes d'adaptation induit par une suralimentation chez l'Homme

Obesity is a chronic multifactorial disease, leading to many pathologies and whose increase in prevalence is reaching epidemic proportions. The energy imbalance (high intakes vs. low expenditures) leads to excess energy storage in specialized tissues but can lead, in pathological obesity, to ectopic storage leading to numerous metabolic disorders. Given the low success of current strategies to improve the metabolic parameters of people with obesity, it has become necessary to find therapeutic alternatives. In order to answer this question, Pr. Laville and his team decided to test the impact of a grape polyphenol supplementation on the appearance of metabolic disorders induced by one month of overnutrition rich in lipids and fructose. During my thesis, I was able to demonstrate that this type of overnutrition induces weight gain, fat mass and significantly alters insulin sensitivity in our healthy volunteers. However, polyphenol supplementation did not prevent fat gain or changes in insulin sensitivity. Fat mass gain was observed in both depots (subcutaneous and visceral) in both sexes. However, polyphenol supplementation did not limit these changes in men. In women, we noticed that the polyphenols made it possible to reduce gynoid fat mass gain, which resulted in a smaller increase in the size of the cells of this depot. Anthropometric changes are accompanied by molecular alterations. We observed this through analysis of the transcriptome by RNA-sequencing, carried out on biopsies of subcutaneous adipose tissue in the cohort of men. Indeed, the nutritional intervention led to a remodeling of genes involved in lipid metabolism, the modulation of the extracellular matrix and angiogenesis. Polyphenol supplementation increased the expression of genes related to oxidative phosphorylation and mitochondria, in addition to lipid metabolism. On the other hand, polyphenols had an inhibitory effect on angiogenesis, confirmed by immunohistochemistry. This impact on angiogenesis seems to involve certain polyphenols such as ...