RELATIONSHIPS OF PPAR-GAMMA AND PPAR-GAMMA-2 MESSENGER-RNA LEVELS TO OBESITY, DIABETES AND HYPERINSULINEMIA IN RHESUS-MONKEYS

OBJECTIVE: To examine the expression of peroxisome proliferator-activa ted receptor gamma (PPAR gamma) together with CCAT/enhancer binding pr otein alpha (C/EBP alpha), lipoprotein lipase (LPL) and glucose transp orter (GLUT4) mRNA in adipose tissue of rhesus monkeys in relation Pa obesity, DESIGN: Cloning of the PPAR gamma 1 and gamma 2 cDNAs and ana lysis of PPAR gamma, C/EBP alpha, LPL and GLUT4 mRNA levels in the adi pose tissue of lean and obese monkeys. SUBJECTS: 28 rhesus monkeys (Ma caca mulatta) with a wide pangs of body weights (9.2-22.6kg) and with or without type 2 diabetes, MEASUREMENTS: Sequence of PPAR gamma 1 and gamma 2, Tissue distribution of PPBR gamma 1 and gamma 2, The mRMA le vels of PPAR gamma, C/EBP alpha, LPL and GLUT4 in adipose tissue, The Patio of PPAR gamma 2 mRNA to total PPAR gamma mRNA. RESULTS: The monk ey PPAR gamma 2 protein showed 99% identity with the human protein, PP AR gamma 1 mRNA was shown to be expressed in various tissues and most abundantly in adipose tissue. PPAR gamma 2 existed mainly in adipose t issue. A significant correlation between the ratio of PPAR gamma 2 mRN A to fetal PPAR gamma mRNA and obesity was observed, whereas fetal PPA R gamma mRNA levels showed no significant relationships to obesity. Th ere was also a significant relationship between the ratio of PPAR gamm a 2 mRNA to total PPAR gamma mRNA and fasting plasma insulin concentra tion. The mRNA levels of C/EBP alpha, LPL and GLUT4 were highly correl ated to that of total PPAR gamma mRNA. They were also significantly co rrelated To the mRNA levels ob: PPAR gamma 1 and PPAR gamma 2. CONCLUS IONS:The ratio of PPAR gamma 2 mRNA to total PPAR gamma mRNA is relate d to obesity in the rhesus monkey and mRNA expression of PPAR gamma 1, PPAR gamma 2, C/EBP alpha, LPL skid GLUT4 appear to be coordinated in vivo.