Thiazolidinediones repress ob gene expression in rodents via activation of peroxisome proliferator-activated receptor gamma

The ob gene product, leptin, is a signaling factor regulating body weight and energy balance, ob gene expression in rodents is increased in obesity and is regulated by feeding patterns and hormones, such as insulin and glucocorticoids, In humans with gross obesity, ob mRNA levels are higher, but other modulators of human ob expression are unknown, In view of the importance of peroxisome proliferator-activated receptor gamma (PPAR gamma) in adipocyte differentiation, we analyzed whether ob gene expression is subject to regulation by factors activating PPARs, Treatment of rats with the PPAR alpha activator fenofibrate did not change adipose tissue and body weight and had no significant effect on ob mRNA levels, However, administration of the thiazolidinedione BRL49653, a PPAR gamma ligand, increased food intake and adipose tissue weight while reducing ob mRNA levels in rats in a dose-dependent manner, The inhibitory action of the thiazolidinedione BRL49653 on ob mRNA levels was also observed in vitro, Thiazolidinediones reduced the expression of the human ob promoter in primary adipocytes, however, in undifferentiated 3T3-L1 preadipocytes lacking endogenous PPAR gamma, cotransfection of PPAR gamma was required to observe the decrease, In conclusion, these data suggest that PPAR gamma activators reduce ob mRNA levels through an effect of PPAR gamma on the ob promoter.