Both genetic and pharmacological studies raise the possibility that a primary increase in the amount or activity of peroxisomal proliferator-activated receptor γ (PPARγ) in adipocytes could play a role in common types of human obesity. Using real-time RT-PCR assays we examined the relationship between body mass index (BMI) and PPARγ isoform expression in freshly isolated human adipocytes. There were no consistent differences in the expression of either PPARγ1 mRNA or PPARγ2 mRNA between omental and sc adipocytes. In a group of 17 subjects (BMI range, 17-34 kg/m2) there was a strong and highly significant inverse correlation (r = -0.68; P < 0.005) between PPARγ1 mRNA expression in adipocytes and BMI, whereas no significant relationship was apparent for PPARγ2. In an independent study PPARγ1 mRNA levels were decreased (1.1 ± 0.1 vs. 3.7 ± 0.8 arbitrary units;P < 0.01) in adipocytes from morbidly obese (BMI, 50.6 ± 14.1 kg/m2) vs. lean (BMI, 21.1 ± 1.0 kg/m2) subjects. In contrast, there was a significant increase in the expression of PPARγ2 mRNA levels between the morbidly obese and lean groups (1.7 ± 0.2 vs. 1.1 ± 0.2 arbitrary units; P < 0.05). Treatment of isolated human adipocytes with TNFγ resulted in a significant decrease in both PPARγ1 and PPARγ2 mRNA levels [40.6 ± 5.5% relative to control (P = 0.01) and 60.9 ± 24.8% (P = 0.02) respectively]. The strong inverse relationship between BMI and PPARγ1 expression in human adipocytes is striking and may represent part of an autoregulatory mechanism restraining the expansion of individual adipocytes in states of positive energy balance. On the other hand, the increase in PPARγ2 observed in adipocytes of morbidly obese individuals suggests a potential pathogenic effect of this isoform in promoting fat acquisition. Although an autocrine effect of the enhanced TNFγ secretion seen with increasing obesity might play a role in the changes in PPARγ1, this would not provide an explanation for the different relationship of PPARγ2 to adiposity. The significance of the divergent effect of human adiposity on the two isoforms will require a greater understanding of the differential properties of the two isoforms and of the differences in the functions of their respective regulatory elements.
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Clinical Biochemistry
- Biochemistry, medical