The influence of dietary lipids on mitochondrial hydrogen peroxide production in liver of calorie restricted mice

Abstract

Calorie restriction (CR) has been shown to delay the onset of age‐related diseases and prolong life spans in a variety of species. CR reduces mitochondrial reactive oxygen species production, attenuates oxidative damage and alters membrane composition towards saturation. This has led to a theory that changes in membrane saturation are central to the actions of CR. As a first step towards testing this theory, C57BL/6 mice were assigned to 3 dietary groups (control and two CR groups) and fed AIN‐93G diets at either 95% (control) or 60% (CR) of ad libitum. To manipulate membrane composition, the primary dietary fat for the CR groups were either soybean oil (also used in the control diet) or fish oil. The diets were fed for 1 month and then liver mitochondria were isolated for measures of mitochondrial lipid composition, proton leak, and H2O2 production. Results indicate that changes in mitochondrial lipids in the CR mice reflected the dietary lipid source. Body weight was lower (p<0.01) in the soy compared to fish CR mice. Mitochondrial H2O2 production was decreased (p<0.01) in the CR fish group compared to the control and CR soy groups regardless of the substrate used for respiration. The results of this study indicate that decreases in long chain unsaturated fatty acids are not necessary for reduced ROS production with CR. Diets containing fish oil may further decrease ROS production with CR. (Supported by NIH RO1 AG028125)