P-61 - Integration of oxidized lipids in pro-inflammatory metabolic networks targeting obesity and related complications

Abstract

Pathogenesis of obesity and related metabolic diseases is closely associated with redox disbalance and production of oxidized lipids. Oxidized lipids affect all main cell populations in adipose tissue, their adipokine secretion and themselves can act as an active lipokines triggering autocrine and paracrine signaling. Obesity associate adipocyte hypertrophy and M2 to M1 adipose tissue macrophage (ATMs) shift was associated with oxidized lipids signaling. Despite large amount of data on the role of oxidized lipids and especially eicosanoids in pro-inflammatory signaling, no unified metabolic networks required for systems medicine data integration are available till now. Based on the literature meta-study, networks of enzymatic and free-radical-driven oxidation were reconstructed for the most abundant polyunsaturated fatty acids (PUFAs) and included 570 reactions covering 480 oxidized lipid species. Using networks of PUFA oxidation as a scaffold, adipocytes and ATMs specific regulatory metabolic networks covering four eicosanoids, namely prostaglandin E2, lipoxin A4, 6,15-deoxy prostaglandin J3, and epoxyeicosatetraenoic acids were reconstructed and enriched to uncover their roles in obesity related adipose tissue lipolysis, cytokines/adipokine production and secretion.