Increased OCT3 expression in adipose tissue with aging: implications for lipid turnover and insulin resistance in women

Abstract Background Catecholamine-stimulated lipolysis is reduced with aging, which may promote adiposity and insulin resistance. Organic cation transporter 3 (OCT3), which is inhibited by estradiol (E2), mediates catecholamine transport into adipocytes for degradation, thus decreasing lipolysis. In this study, we investigate the association between OCT3 mRNA levels in subcutaneous adipose tissue (SAT) from women with aging and markers of insulin resistance. Methods SAT biopsies were obtained from 66 women with or without T2D (19/47 respectively, 22-76 years old, 20.0-40.1 kg/m2). OCT3 mRNA and protein levels were measured for group comparisons and correlation analysis. SAT was incubated with E2 and OCT3 mRNA levels were measured. The associations between OCT3 single nucleotide polymorphisms (SNPs) and diabetes-associated traits were assessed. Results OCT3 mRNA and protein levels in SAT were increased with aging. SAT from postmenopausal women had higher levels of OCT3 than premenopausal women, and there was a dose-dependent reduction in OCT3 mRNA levels in SAT treated with E2. OCT3 mRNA levels were negatively associated with markers of insulin resistance, and ex vivo lipolysis. OCT3 SNPs were associated with BMI, waist-hip-ratio, and circulating lipids (e.g. triglycerides). Conclusion OCT3 mRNA and protein levels in SAT were increased with aging, and mRNA levels were negatively associated with markers of insulin resistance. E2 incubation downregulated OCT3 mRNA levels, which may explain lower OCT3 mRNA levels in premenopausal compared to postmenopausal women. High OCT3 mRNA and protein levels may result in increased catecholamine degradation, which may account for the reduction in adipose tissue lipolysis observed with aging.