Peroxisome proliferator activated receptor-gamma, leptin and tumor necrosis factor-alpha mRNA expression during very low calorie diet in subcutaneous adipose tissue in obese women

PPAR gamma, leptin and TNF alpha are three major factors that play a key role in influencing adipocyte differentiation and both adipose tissue function and metabolism. However, the regulation of these three genes during a dynamic period of weight loss is unknown. We therefore investigated the concomitant regulation of the mRNA expression of PPAR gamma, leptin and TNF alpha in adipose tissue during a 21-day very low calorie diet (VLCD) in 12 non-diabetic obese women.The mRNA levels of PPAR gamma, leptin and TNF alpha were quantified by quantitative RT-competitive PCR in abdominal subcutaneous adipose tissue before and during VLCD (940 kcal/day).VLCD induced weight loss (approximately 6 kg) and improved insulin sensitivity. Simultaneously, VLCD induced the reduction in the adipose tissue mRNA abundances of PPAR gamma (-13%, p0.05) and of leptin (-58%, p0.005), whereas TNF alpha mRNA levels increased (+78%, p0.005). PPAR gamma and leptin mRNA levels were correlated before (r = 0.778, p0.01) and after VLCD (r = 0.797, p0.01). Serum HDL-cholesterol concentrations were positively associated with PPAR gamma (r = 0.696, p0.03) and leptin (r = 0.806, p0.01) mRNA levels.The increase in TNF alpha mRNA levels suggested that a local increased expression of this cytokine in adipose tissue might play a role in the control of the fat mass during weight loss. PPAR gamma and leptin mRNA levels were positively associated both before and after VLCD, suggesting that common regulatory mechanism(s) might control their expression. More strikingly, we found strong positive correlations between circulating HDL-cholesterol and both PPAR gamma and leptin mRNA levels, suggesting the existence of physiological links between circulating lipoprotein metabolism and adipose tissue function.