PPARγ2 protects against obesity by means of a mechanism that mediates insulin resistance

Abstract

Many studies have focused on the physiological parameters and genetic predisposition of subjects presenting both obesity and insulin resistance (IR) and it has been suggested that the peroxisome proliferator-activated receptor gamma 2 (PPARgamma2) Pro12Ala variant may contribute to the observed variability in insulin sensitivity. We investigated whether the PPARgamma2 mRNA expression levels are associated with IR in morbid obesity in adipose and muscle tissues. In this study, tissue biopsies were obtained from 26 morbidly obese (MO) patients and eight controls. The MO patients were divided into two groups: those with a low homeostasis model assessment of IR (HOMA-IR < 5) (MO-nonIR) and those with a high HOMA-IR (HOMA-IR > or = 8) (MO-IR). PPARgamma1, PPARgamma2 and aP2 mRNA expression levels were measured using quantitative RT-PCR. The study found that PPARgamma2 mRNA expression in visceral adipose tissue (VAT) was significantly lower in the MO patients (P = 0.002) than the controls. Moreover, the PPARgamma2 mRNA expression was lower in VAT (P < 0.05) and muscle tissue (P < 0.01), and higher in subcutaneous adipose tissue (SAT) (P < 0.01) in the MO-IR than the MO-nonIR group. By contrast, PPARgamma1 mRNA expression levels were not dependent on IR. Finally, the MO patients showed a significant negative correlation between PPARgamma2 mRNA expression and IR (r = -0.396, P = 0.020) in VAT and a positive correlation in SAT (r = 0.826, P < 0.001). The variable that best explained the IR was PPARgamma2 mRNA expression in SAT (P = 0.002). These data show that PPARgamma2 mRNA is expressed differently in the two types of MO patients and is associated with IR.