THE THIAZOLIDINEDIONE INSULIN SENSITIZER, BRL-49653, INCREASES THE EXPRESSION OF PPAR-GAMMA AND AP(2) IN ADIPOSE-TISSUE OF HIGH-FAT-FED RATS

The effects of the thiazolidinedione insulin sensitiser BRL 49653 on p lasma leptin concentrations and on epididymal fat OB, PPAR-gamma and a P(2) mRNA expression were examined in high-fat-fed and high-carbohydra te-fed adult Wistar rats. Diets were given for 4 weeks, with BRL 49653 (10 mu mol/kg/day) administered by oral gavage for the last 4 days. T reatment with BRL 49653 reduced plasma leptin concentrations in high-f at-fed rats from 2.34 +/- 0.19 (n=9) to 1.42 +/- 0.09 (n=9) ng/ml (p<0 .001). Plasma leptin was unaffected by BRL 49653 in the high-carbohydr ate-fed rats. There was no difference in OB mRNA expression between hi gh-fat-fed and high-carbohydrate-fed rats, with or without treatment. PPAR-gamma and aP(2) mRNA expression were significantly increased in t he high-fat-fed rats treated with BRL 49653 (p<0.01 and p<0.001 respec tively), but not in carbohydrate-fed rats. (C) 1996 Academic Press