Relationships of PPARgamma and PPARgamma2 mRNA levels to obesity, diabetes and hyperinsulinaemia in rhesus monkeys.

OBJECTIVE

To examine the expression of peroxisome proliferator-activated receptor gamma (PPARgamma) together with CCAAT/enhancer binding protein alpha (C/EBPalpha), lipoprotein lipase (LPL) and glucose transporter (GLUT4) mRNA in adipose tissue of rhesus monkeys in relation to obesity.

DESIGN

Cloning of the PPARgamma1 and gamma2 cDNAs and analysis of PPARgamma, C/EBPalpha, LPL and GLUT4 mRNA levels in the adipose tissue of lean and obese monkeys.

SUBJECTS

28 rhesus monkeys (Macaca mulatta) with a wide range of body weights (9.2-22.6 kg) and with or without type 2 diabetes.

MEASUREMENTS

Sequence of PPARgamma1 and gamma2. Tissue distribution of PPARgamma1 and gamma2. The mRNA levels of PPARgamma, C/EBPalpha, LPL and GLUT4 in adipose tissue. The ratio of PPARgamma2 mRNA to total PPARgamma mRNA.

RESULTS

The monkey PPARgamma2 protein showed 99% identity with the human protein. PPARgamma1 mRNA was shown to be expressed in various tissues and most abundantly in adipose tissue. PPARgamma2 existed mainly in adipose tissue. A significant correlation between the ratio of PPARgamma2 mRNA to total PPARgamma mRNA and obesity was observed, whereas total PPARgamma mRNA levels showed no significant relationships to obesity. There was also a significant relationship between the ratio of PPARgamma2 mRNA to total PPARgamma mRNA and fasting plasma insulin concentration. The mRNA levels of C/EBPalpha, LPL and GLUT4 were highly correlated to that of total PPARgamma mRNA. They were also significantly correlated to the mRNA levels of PPARgamma1 and PPARgamma2.

CONCLUSIONS

The ratio of PPARgamma2 mRNA to total PPARgamma mRNA is related to obesity in the rhesus monkey and mRNA expression of PPARgamma1, PPARgamma2, C/EBPalpha, LPL and GLUT4 appear to be coordinated in vivo.