OBELEX

Obesity is associated with the development of metabolic diseases including diabetes subject 2. Obesity leads to a decrease in life expectancy by favoring various cellular processes that lead to aging. It is well known that aging is accompanied by increased visceral fat accumulation and the development of metabolic complications. Both aging and obesity have been identified as pathologies of chronic inflammatory origin of low Degree. Inflammation associated with aging (inflammaging) has been considered as a risk factor for most age-related diseases and thus for morbidity/mortality in the elderly. However, the underlying mechanisms have not been fully established.

The resolution of inflammation is an active process involving the production of pro-resolving lipid mediators such as lipoxins, resolvins, protectins and maresins. We hypothesize that chronic inflammation associated with obesity and aging could be result of an insufficient production of these pro-resolving lipid mediators, especially in adipose tissue. On the other hand, it has been seen that the expression of an altered transcriptional patron saint could also be a factor in the development inflammation associated with obesity and aging. Therefore, the first goal of this project is to characterize the mechanisms involved in the chronic inflammation that occurs in obesity and aging.

Given that omega-3 polyunsaturated fatty acids (n-3 PUFA) are precursors in the synthesis of pro-resolving lipid mediators and that they also participate in transcriptional regulation, our project proposes that long-term dietary supplementation with n-3 PUFA, alone or in combination with regular physical exercise, could promote resolve local and systemic inflammation associated with obesity and aging. Therefore, we propose to study the pathophysiological mechanisms of inflammation in aging and the potential benefits of long-term dietary supplementation with DHA, an n-3 PUFA, as well as physical exercise in mice with obesity induced by per diem expenses. In this model, we will focus on the study of the biology and metabolism of adipose tissue (white, beige and brown) with special emphasis on the characterization of transcriptional patron saint and pro-resolving lipid mediators of inflammatory nature, as well as their impact on glyco-lipid metabolism. Pathophysiological alterations of muscle and gastrointestinal tract (liver, intestinal function and its microbiota) will also be studied.

On the other hand, a nutritional intervention study in overweight/obese post-menopausal women will also be carried out to characterize the effects of the administration of a DHA-rich dietary supplement and/or a progressive resistance physical exercise program. Their actions on weight loss and fat mass, insulin sensitivity and inflammatory markers of adipose tissue will be studied as well as the profile of gene, miRNAs and lipidomic expression. Finally, in vitro mechanistic programs of study will be performed in human adipocytes, alone or in co-culture with macrophages, muscle and intestinal cells that will allow a better characterization of the interactions between these tissues in the context of obesity and inflammatory pathologies.