The PPARγ ligand rosiglitazone influences triacylglycerol metabolism in non-obese males, without increasing the transcriptional activity of PPARγ in the subcutaneous adipose tissue

PPAR gamma is obligatory for fat mass generation and is thought to determine the amount of TAG stored per fat cell. We investigated whether ligand availability for PPAR gamma is rate limiting in fat mass generation and substrate metabolism. Twenty healthy men (20-29 years) were randomly assigned to receive the PPAR gamma ligand rosiglitazone (RSG) (8 mg/d) (n 10) or a placebo (n 10) during a stay of 7d in a respiration chamber. Food intake was ad libitum, resulting in positive energy balances of 32.2MJ (placebo) and 44.7MJ (RSG). Fat cell size and expression of PPAR gamma, adipocyte fatty acid-binding protein (aP2), adipsin, adiponectin and fasting-induced adipose factor (FIAF) were determined in subcutaneous abdominal fat biopsies. The total amount of fat stored and the amount of TAG per fat cell were not different between groups. For the entire group, fat cell size was decreased after overeating (P=0.02). FIAF mRNA levels were decreased after overeating in the RSG group (P=0.01), with a trend towards a decrease in the placebo group. Unexpectedly, RSG treatment did not influence the expression levels of PPAR gamma and of the PPAR gamma responsive genes aP2, adiponectin and adipsin. In addition, RSG resulted in a larger increase in plasma TAG during overeating than placebo treatment. These results Suggest that in healthy, non-obese males the PPAR gamma ligand RSG influences TAG metabolism, independent of its PPAR gamma transcriptional activity in the subcutaneous adipose tissue.