White adipose tissue (WAT) is a complex organ with both metabolic and endocrine functions. Dysregulation of all of these functions of WAT, together with low-grade inflammation of the tissue in obesity, contributes to the development of insulin resistance and type 2 diabetes. Omega-3 polyunsaturated fatty acids (PUFA) of marine origin play an important role in resolution of inflammation and exert beneficial metabolic effects. Using experiments in mice and overweight/obese type 2 diabetic patients we elucidated the structures of novel members of fatty acid esters of hydroxy fatty acids (FAHFA) - lipokines derived from docosahexaenoic (DHA) and linoleic acid, which were present in serum and WAT after omega-3 PUFA supplementation. These compounds contained DHA esterified to 9- and 13-hydroxyoctadecadienoic acid (HLA) or 14-hydroxydocosahexaenoic acid (HDHA), termed 9-DHAHLA, 13-DHAHLA, and 14-DHAHDHA, and were synthesized by adipocytes at concentrations comparable to those of protectins and resolvins derived from DHA in WAT. 13-DHAHLA exerted anti-inflammatory and pro-resolving properties while reducing macrophage activation by lipopolysaccharide and enhancing the phagocytosis of zymosan particles. Our results document the existence of novel lipid mediators, which are involved in the beneficial anti-inflammatory effects attributed to omega-3 PUFA, in both mice and humans.
- Received March 23, 2016.
- Accepted June 6, 2016.
- © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.