Effects of ciglitazone on energy balance, thermogenesis and brown fat activity in the rat.

Young male rats were treated with vehicle or ciglitazone (150 mg/kg/day, intragastric) for 8 or 14 days. Drug treatment did not affect food intake but reduced body weight and energy gains over 14 days, and significantly depressed energetic efficiency. Energy expenditure and resting oxygen consumption (VO2), when corrected for body size, were elevated in ciglitazone-treated rats, but the difference in VO2 was abolished by treatment of the animals with a beta-adrenergic antagonist (propranolol). The acute thermic response (postprandial rise in VO2) to a fat meal was similar for both groups, but the response to carbohydrate ingestion was greater in ciglitazone-treated rats (18%) than controls (11.5%). The mass of interscapular brown adipose tissue was not affected by drug treatment, but its protein content was increased and its thermogenic activity (mitochondrial purine nucleotide binding) was elevated by 25% after chronic treatment with ciglitazone. These results indicate that ciglitazone enhances thermogenesis via sympathetic activation of brown adipose tissue, probably as a result of improved insulin sensitivity.