The mechanism by which PHBs affect OPA1 processing remains to be determined

nthesis. As genes involved in cholesterol excretion or HDL uptake were not affected by GW 501516 site 11b-HSD1 inhibition in WNIN/Ob obese rats, possibly, decreased expression of cholesterol biosynthetic genes might have contributed to the amelioration of hypercholesterolemia in this model. Although CBX decreased plasma HDL cholesterol in obese rats, it may not be pro-atherogenic, as the levels were brought down to those observed in lean rats. Thus, the decreased 12 11beta-HSD1 and Obesity plasma HDL-cholesterol level in obese rats is the consequence of cholesterol removal from body. This phenomenon is considered to be anti-atherogenic. Body composition, adipose tissue morphology, fibrosis and gene expression Previous studies have reported that cortisol is essential for preadipocyte differentiation. 11bHSD1 plays an important role in adipose tissue physiology, as it increases local corticosterone levels. Adipose-specific over- expression of 11b-HSD1 in mice, results in increased visceral fat mass due to adipocyte- hypertrophy, where as 11b-HSD1 knock-out mice are resistant to diet-induced obesity. Elevated 11bHSD1 activity was observed in adipose tissue of obese rodent models and in human obesity.11b-HSD1 inhibition by CBX or selective inhibitors resulted in decreased fat mass in dietinduced obesity and rodent models of genetic obesity. In line with these observations, 11b-HSD1 inhibition significantly decreased body fat mass in WNIN/Ob lean and obese rats. As observed in previous studies, 11b-HSD1 inhibition decreased adipocyte- hypertrophy in obese rats. To further explain the molecular mechanisms involved the adipose tissue loss, we have studied the expression of beta3adrenergic receptor gene, which stimulates lipolysis in adipose tissue. b3-AR gene expression is shown to be lower in obese rodent models and its activation leads to fat loss and amelioration of obesity- induced insulin resistance. Recent studies on 11b-HSD1 knock-out mice also showed increased betaadrenergic signaling in visceral adipose tissue. In line with the previous observations, WNIN/Ob obese rats have reduced b3-AR gene expression in adipose tissue. An increased trend in b3-AR gene expression was also observed in adipose tissue of CBXtreated obese rats, which could be one of the mechanisms involved in fat loss observed in the obese rats. Notably, CBX induced severe fat- loss in lean rats as compared with that observed in obese rats. This might be due to the fact that 11b-HSD1 inhibition by CBX was higher in adipose depots of lean rats than that of obese rats. Another possible reason for the observed excessive fat- loss in lean rats might be due to decreased food intake by CBX administration, which was not affected in obese rats. As in case of obese rats, a trend towards increase was also observed in adipose tissue- b3-AR gene expression of CBX-treated lean rats. Elevated b3-AR expression by CBX might have resulted in lipolysis and fat mobilization in lean rats. To our knowledge, this is the first study to show the effect of 11b-HSD1 inhibition on adipose tissue b3AR gene expression. Recent studies have shown that extracellular matrix plays an important role in adipose tissue physiology. Adipose tissue fibrosis is reported in obese animal models and humans. Amelioration of obesity and insulin resistance is known to decrease adipose tissue fibrosis in animal models of obesity. So far, no studies have reported the effect of 11b-HSD1 inhibition on adipose tissue fibrosis in obese