Adaptive effects of prolonged mitochondrial‐targeted catalase on adipocyte differentiation

Abstract

One cause of obesity is an increase in the total number adipocytes by hyperplasia. To increase fat cell number, adipocyte precursors undergo differentiation into mature fat cells, a process which requires reactive oxygen species (ROS). ROS are generated in the mitochondria during oxidative phosphorylation, and previous studies have shown that short‐term treatment with mitochondria‐targeted antioxidants can reduce adipogenesis. This suggests that antioxidant therapy might be useful to treat obesity, although the efficacy of antioxidants for long‐term treatment has not been investigated. Mice that have catalase targeted to mitochondria (mCAT mice) have increased levels of the antioxidant enzyme throughout life. We tested whether mCAT mice would display reduced fat pad mass or body weight due to a reduction in mitochondrial hydrogen peroxide. At 12 weeks of age, mCAT mice showed no significant decrease in size or weight of subcutaneous fat depots compared to wild‐type mice, which suggests that mCAT pre‐adipocytes were able to bypass the requirement for ROS and differentiate normally. To test this, we isolated preadipocytes from subcutaneous fat pads of mCAT mice and compared their differentiation profiles to cells transiently transfected with a plasmid encoding mitochondrial catalase. As expected, short‐term antioxidant treatment resulted in little to no differentiation. Although preadipocytes from mCAT mice differentiated more slowly in culture, they were ultimately able to reach full differentiation. Gene expression profiles of regulatory proteins that function during differentiation in cells with short‐term antioxidant treatment were different than those with long‐term exposure. Current work involves understanding how these gene expression changes are directly affected by mitochondrial hydrogen peroxide.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.