Elevated free fatty acids and impaired adiponectin bioactivity contribute to reduced SOD2 protein in monocytes of type 2 diabetes patients.

Type 2 diabetes (T2D) is characterized by increased oxidative stress contributing to the development of cardiovascular disease (CVD). Monocytes are critically important in the pathogenesis of CVD and antioxidant enzymes like superoxide dismutase (SOD2) protect these cells from excessive reactive oxygen species (ROS). Adiponectin is an adipocyte-derived protein with atheroprotective function and the effect of adiponectin on monocyte SOD2 was analyzed herein. Adiponectin upregulated SOD2 mRNA and dose- and time-dependently induced SOD2 protein in primary human monocytes. Elevated systemic free fatty acids (FFA) are commonly found in T2D patients and palmitic acid as well as oleic acid reduced monocyte SOD2 protein. Adiponectin mediated upregulation of SOD2, however, was not affected by FFA incubation. SOD2 protein was reduced in T2D monocytes compared to monocytes of age- and body mass index-matched healthy controls. Adiponectin still induced SOD2 in T2D monocytes but efficiency tended to be reduced. In summary this study indicates that elevated systemic free fatty acids and impaired adiponectin activity contribute to reduced SOD2 and most likely increased oxidative stress in T2D monocytes.