The Inhibitory Effect of Testosterone on PPARγ-induced Adipogenesis

Abstract

Background: Peroxisome proliferator-activated receptor γ (PPARγ) plays a major role in adipocyte differentiation. Testosterone is well known for inhibiting adipocyte metabolism in men. To investigate the inhibitory mechanism of testosterone on adipogenesis, this study evaluated the effects of testosterone on PPARγ expression and activity in adipocytes using in vitro approaches. Methods: After differentiated 3T3-L1 adipocytes were treated with PPARγ agonist troglitazone and sex hormone testosterone, the effects of testosterone on troglitazone-induced triglyceride accumulation and expression of genes involved in adipogenesis were investigated. We also inves-tigated whether testosterone regulates troglitazone-induced PPARγ reporter activity in 3T3-L1 preadipocytes. Results: Testosterone decreased triglyceride accumulation in differentiated 3T3-L1 cells compared with the vehicle treated control group. Testosterone also decreased the expression of PPARγ mRNA as well as PPARγ dependent adipocyte-specific genes, such as adipocyte fatty acid binding protein and tumor necrosis factor α. Moreover, testosterone treatment inhibited triglyceride accumulation, and the expression of PPARγ and adipocyte-specific genes caused by troglitazone in differentiated 3T3-L1 cells. Testosterone decreased troglitazone-induced PPARγ reporter activity. Also, treatment with testosterone led to an inhibition of troglitazone-induced PPARγ reporter activity in PPARγ and androgen receptor (AR) expressed 3T3-L1 preadipocytes. Conclusion: These results suggest that testosterone interferes with the actions of PPARγ on adipogensis by an AR-dependent component. In addition, this study may have provided valuable molecular and biological insights regarding testosterone therapy in obese hypogonadal men.