Aging has been shown to have an effect on the capacity to differentiate preadipocytes and on the expression of some genes expressed in adipose tissue. The mRNA levels of adipocyte differentiation-related genes were examined in rhesus monkeys (Macaca Mulatta) ranging in age from 7 to 30 years. The effect of aging on the expression of peroxisome proliferator activated receptor gamma (PPAR gamma) adipocyte determination- and differentiation-dependent factor 1/sterol regulatory element binding protein I (ADD1/SREBP1) CCAAT/enhancer binding protein alpha (C/EBP alpha) lipoprotein lipase (LPL) GLUT4 glucose transporter and adipsin were examined by slot blot analysis. Significant inverse correlations were observed between age and the mRNA levels of PPAR gamma, ADD1/SREBP1, LPL, and GLUT4. The coordinate downregulation of these genes may be linked to the declining fat mass of senescent animals. There was no correlation between age and the mRNA levels of adipsin. The mRNA levels of these genes were not correlated to body weight or fasting plasma insulin. These findings indicate that aging may have an effect on the adipocyte differentiation program and this effect appears to be gene specific.

Thiazolidinediones (TZD) have been shown to have anti-diabetic effects including the ability to decrease fasting hyperglycemia and hyperinsulinemia, increase insulin-mediated glucose disposal rate (M) and decrease hepatic glucose production, but the mechanisms of action are not well established. To determine whether a TZD (R-102380, Sankyo Company Ltd., Tokyo, Japan) could improve insulin action on skeletal muscle glycogen synthase (GS), the rate-limiting enzyme in glycogen synthesis, 4 insulin-resistant obese monkeys were given 1 mg/kg/day R-102380 p.o. for a 6-week period. Skeletal muscle GS activity and glucose 6-phosphate (G6P) content were compared between pre-dosing and dosing periods before and during the maximal insulin-stimulation of a euglycemic hyperinsulinemic clamp. Compared to pre-dosing, insulin-stimulated GS activity and G6P content were increased by this TZD: GS independent activity (p = 0.02), GS total activity (p = 0.005), GS fractional activity (p = 0.06) and G6P content (p = 0.02). The change in GS activity induced by in vivo insulin (insulin-stimulated minus basal) was also increased by this TZD: GS independent activity (p = 0.03) and GS fractional activity (p = 0.04). We conclude that the TZD R-102380 improves insulin action at the skeletal muscle in part by increasing the activity of glycogen synthase. This improvement in insulin sensitivity may be a key factor in the anti-diabetic effect of the thiazolidinedione class of agents.

OBJECTIVE: To examine the expression of peroxisome proliferator-activated receptor γ (PPARγ) together with CCAAT/enhancer binding protein α (C/EBPα), lipoprotein lipase (LPL) and glucose transporter (GLUT4) mRNA in adipose tissue of rhesus monkeys in relation to obesity. DESIGN: Cloning of the PPARγ1 and γ2 cDNAs and analysis of PPARγ, C/EBPα, 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 PPARγ1 and γ2. Tissue distribution of PPARγ1 and γ2. The mRNA levels of PPARγ, C/EBPα, LPL and GLUT4 in adipose tissue. The ratio of PPARγ2 mRNA to total PPARγ mRNA. RESULTS: The monkey PPARγ2 protein showed 99% identity with the human protein. PPARγ1 mRNA was shown to be expressed in various tissues and most abundantly in adipose tissue. PPARγ2 existed mainly in adipose tissue. A significant correlation between the ratio of PPARγ2 mRNA to total PPARγ mRNA and obesity was observed, whereas total PPARγ mRNA levels showed no significant relationships to obesity. There was also a significant relationship between the ratio of PPARγ2 mRNA to total PPARγ mRNA and fasting plasma insulin concentration. The mRNA levels of C/EBPα, LPL and GLUT4 were highly correlated to that of total PPARγ mRNA. They were also significantly correlated to the mRNA levels of PPARγ1 and PPARγ2. CONCLUSIONS: The ratio of PPARγ2 mRNA to total PPARγ mRNA is related to obesity in the rhesus monkey and mRNA expression of PPARγ1, PPARγ2, C/EBPα, LPL and GLUT4 appear to be coordinated in vivo .