Inhibition of adipogenesis by Tempol in 3T3-L1 cells

Obesity is highly associated with an increased risk of serious health conditions including hypertension, cardiovascular disease, diabetes, and cancer. Changes in redox status with increased oxidative stress have been linked with obesity. Previous studies have shown that administration of the antioxidant Tempol in the food of mice prevents obesity, causing significant weight loss without toxicity. To gain a better understanding of the molecular mechanism(s) underlying this effect, the influence of Tempol on the differentiation of mouse 3T3-L1 preadipocytes was studied. Tempol inhibited differentiation of 3T3-L1 cells, resulting in a reduction in cellular lipid storage, down-regulation of protein levels of key adipogenesis transcription factors (PPARgamma and PPARalpha), down-regulation of prolyl hydroxylase, and up-regulation of HIF-1alpha. Mice on a Tempol diet demonstrated reduced systemic levels of IGF-1, in qualitative agreement with in vitro observations in 3T3-L1 cells, which also showed lower IGF-1 levels as a result of Tempol treatment. These results show that treatment of 3T3-L1 cells with Tempol inhibits the expression of key adipogenesis factors, adipose differentiation, and lipid storage and may underlie, at least in part, some of the in vivo effects of Tempol on body weight.