MED-OMEGA3-PLUS

Obesity is considered a chronic inflammatory pathology of low Degree. Furthermore, this inflammatory state associated with obesity has been proposed as a link to several obesity-associated disorders such as insulin resistance, cardiovascular disease and metabolic syndrome. Obesity has also been associated with a higher prevalence and worse prognosis of inflammatory bowel disease. Moreover, obesity-associated neuroinflammation has been linked to the development of central insulin resistance, neurocognitive disorders and Alzheimer's disease. It is now known that the resolution of inflammation is an active process involving some local bioactive mediators produced in the final phase of inflammatory processes, such as resolvins, protectins and maresin (derived from omega-3 fatty acids).

Our hypothesis is that chronic inflammation associated with obesity and the development of metabolic, intestinal and neurocognitive disorders is accompanied by a deficit in the levels of these pro-resolving lipid mediators of inflammation. Therefore, the first goal of the present study is to determine whether there are differences in the levels of pro-resolving lipid mediators of inflammation in adipose tissue and intestinal mucosa between lean and obese subjects. On the other hand, and taking into account the relationship between neuroinflammation and Alzheimer's disease, we also propose to analyze whether the development of Alzheimer's disease is associated with a reduction in the levels of these pro-resolving mediators.

Moreover, treatment with these lipid mediators could be a potential therapy to combat chronic inflammation associated with obesity. Therefore, we also intend to determine the efficacy of oral administration of maresin 1 (MaR1) in obese mice on adipose tissue inflammation and insulin resistance, on intestinal function, and on neuroinflammation and potential cognitive impairment associated with obesity. Its actions on the intestinal microbiota will also be analyzed.

Finally, programs of study will be performed in cell cultures of adipocytes and Caco-2 cells, a model of human intestinal epithelium, in order to deepen the mechanisms of action of MaR1 and its ability to reverse the functional alterations induced by inflammation.