Effects of omega-3 fatty acids in bioactive metabolome in macrophages of human blood and diabetic mice scar tissue

Abstract

Delayed wound healing is a common complication of cancer and diabetes, increasing infections, amputations and death. Tissue repair requires the migration of cells into the wounded region and the proliferation of new cells to restore the original density of the tissue. In this process the shift between proinflammatory molecules to proresolution is essential to limit the damage of tissue and allow progression to the next phases. Bioactive metabolome from arachidonic acid (AA, C20:4, É-6), eicosapentaenoic acid (EPA, C20:5, É-3), docosahexaenoic acid (DHA, C22:6, É-3) alter the inflammatory response and resolution of inflammation. It is known that omega-3 fatty acids (É-3) have immunomodulatory effects in physiological and pathophysiological conditions. However, it is not clear the effects of peri-operative use of É-3 fatty acids on tissue repair. Supplementation with É-3 fatty acids alters the membrane composition of phospholipids, thus modifying the production of lipid mediators, such as maresins and resolvins, altering the inflammatory response. So, the aim of the present project is to evaluate the production of bioactive lipids in scar tissue of mice. For that, mice will be separated into three groups: (C) Control; (D) diabetics and (ED) diabetic animals that received 2 g/Kg of body weight of EPA-rich oil. After 4 weeks of EPA-rich oil supplementation, a wound will be induced in back dorsum of the animals, and the tissue will be collected at different time points. Since this project is part of a clinical trial, in development in UK, we will also analyze the production of bioactive lipids by blood macrophages in patients with peri-operative omega-3 nutritional supplementation with colorectal cancer undergoing elective laparoscopic colorectal resection. To investigate the production of lipid mediators, we will perform CG-MS/MS to evaluate more than 30 metabolites derived from AA, EPA and DHA.