| Description |
Uncoupling protein-1 (UCP1) resides in the inner mitochondrial membrane of brown adipose tissue (BAT) and is activated by increased cellular free fatty acids. Activation of UCP1 increases uncoupled mitochondrial respiration. When free fatty acids are oxidized in the mitochondria, mitochondrial endogenous reactive oxygen species (mROS) increase. Whether or not endogenous mROS contribute to the activation of UCP1 and increased uncoupled mitochondrial respiration is not known. We hypothesized that increased endogenous mROS will increase dependency on UCP1 during uncoupled respiration. Mice with adipocyte-specific manganese superoxide dismutase 2 knock out (AdSod2 KO) and age-matched control (CTR) mice were fed high-fat diet (HFD) (45% fat) for 10 weeks. Mitochondrial measurements were conducted using intact mitochondria from brown adipose tissue (BAT). Expression of UCP1 and electron transport chain complexes were determined by western blot. Groups were defined as follows: CTR on normal chow diet (NCD) (n=8), CTR on HFD (n=6), AdSod2 KO on HFD (n=6) and AdSod2 KO on NCD (n=2). We found UCP1-dependent uncoupled respiration in AdSod2 KO HFD mice was significantly decreased compared with CTR HFD mice. Additionally, UCP1 expression decreased in AdSod2 KO HFD compared with CTR HFD mice. AdSod2 KO mice, designed to increase endogenous mROS, do not increase UCP1-dependent respiration, rather UCP1-dependent respiration is decreased. iv Further, AdSod2 KO mice have decreased ability to express UCP1 in HFD conditions compared with diet-matched CTR littermates. |
