The Inhibitory Effect of Testosterone on PPARÎ³-induced Adipogenesis

Jeong, Sunhyo

Abstract

BACKGROUND
Peroxisome proliferator-activated receptor Î³ (PPARÎ³) 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 PPARÎ³ expression and activity in adipocytes using in vitro approaches.
METHODS
After differentiated 3T3-L1 adipocytes were treated with PPARÎ³ 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 investigated whether testosterone regulates troglitazone-induced PPARÎ³reporter 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 PPARÎ³ mRNA as well as PPARÎ³ dependent adipocyte-specific genes, such as adipocyte fatty acid binding protein and tumor necrosis factor Î±. Moreover, testosterone treatment inhibited triglyceride accumulation, and the expression of PPARÎ³ and adipocyte-specific genes caused by troglitazone in differentiated 3T3-L1 cells. Testosterone decreased troglitazone-induced PPARÎ³ reporter activity. Also, treatment with testosterone led to an inhibition of troglitazone-induced PPARÎ³ reporter activity in PPARÎ³ and androgen receptor (AR) expressed 3T3-L1 preadipocytes.
CONCLUSION
These results suggest that testosterone interferes with the actions of PPARÎ³ 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.