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Increased plasma levels of plasminogen activator inhibitor-1 (PAI-1) have been suggested to be a part of the insulin resistance syndrome, and recent data suggest that adipose tissue participates in the production of PAI-1. We examined the expression and insulin regulation of subcutaneous adipose tissue PAI-1 mRNA and its relationship to insulin sensitivity.A cross-sectional study involving five lean (60.0+/-3.1 years, BMI 23.5+/-0.5 kg/m(2)) and six obese nondiabetic men (56.0+/-3.1 years, BMI 30.4+/-0.7 kg/m(2)), and six obese Type 2 diabetic men (61.4+/-3.2 years, BMI 31.8+/-1.0 kg/m(2)).Subcutaneous adipose tissue PAI-1 mRNA and insulin sensitivity were quantified using RT-competitive PCR and euglycemic hyperinsulinemic clamp technique, respectively.Subcutaneous adipose tissue PAI-1 mRNA levels were higher in obese nondiabetic and Type 2 diabetic men than in lean nondiabetic men. PAI-1 mRNA levels decreased in the three groups during a 240-min euglycemic hyperinsulinemic clamp (P0.05 for all groups), and a similar reduction was observed during a 240-min saline control study indicating that adipose tissue PAI-1 gene expression has diurnal variation and is not acutely controlled by hyperinsulinemia. The basal PAI-1 mRNA levels correlated positively with BMI, and waist-to-hip ratio; and negatively with whole-body glucose disposal rate in nondiabetic men.Subcutaneous adipose tissue PAI-1 mRNA expression is increased in obese nondiabetic or in Type 2 diabetic men. Subcutaneous adipose tissue PAI-1 mRNA expression is increased in proportion to visceral obesity and to the level of whole-body insulin resistance. Subcutaneous adipose tissue PAI-1 mRNA expression is not acutely regulated by insulin, and it is subject to a diurnal variation.

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.