Endothelial/Nitric Oxide Regulation of Brown Adipose Tissue Activating Lipokine, 12, 13-diHOME and Its Antiatherogenic Actions

Activation of brown adipose tissue (BAT) has been shown to decrease atherosclerosis due to its systemic actions to improve insulin sensitivity and facilitate weight loss. However, the direct effect of BAT cytokines on vascular arterial function and atherosclerosis has not been studied. We have reported that enhancing insulin’s action on the endothelial cells (EC) by overexpressing IRS1 to the EC on ApoE -/- background (ECIRS1/ApoE-/- mice) greatly increased insulin induced NO production and decreased atherosclerosis. ECIRS1 mice exhibited significant increases in BAT mass and activation when exposed to cold temperature (5°C), in parallel with elevation of BAT lipokine, 12,13-diHOME levels at basal, regular chow (RD) or high fat diet (HFD) compared to wild type mice (WT) by 188±33% and 187±39%, respectively, (P Disclosure K. Park: None. Q. Li: None. M. Lynes: None. H. Yokomizo: None. T. Shinjo: None. R. St-Louis: None. J. Fu: None. C. Rask-Madsen: Research Support; Self; Novo Nordisk A/S. Y. Tseng: Other Relationship; Self; Chugai Pharmaceutical Co., Ltd.. Research Support; Self; MedImmune. G.L. King: Research Support; Self; Sanofi-Aventis.