AI Article Synopsis
- Catecholamine-stimulated lipolysis decreases with age, leading to increased fat accumulation and insulin resistance, linked to the function of OCT3, a transporter inhibited by estradiol (E2).
- The study involved analyzing subcutaneous adipose tissue (SAT) from women of varying ages and diabetes statuses to measure OCT3 mRNA levels and their correlation to insulin resistance.
- Results showed that OCT3 mRNA and protein levels rise with age and postmenopause, but decrease with E2 treatment, suggesting that higher OCT3 levels may impair lipolysis and contribute to insulin resistance in older women.
Article 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 investigated the association of OCT3 mRNA levels in subcutaneous adipose tissue (SAT) with aging and markers of insulin resistance in women.
Methods: SAT biopsies were obtained from 66 women with (19) or without (47) type 2 diabetes (age 22-76 years, 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. Associations between OCT3 single nucleotide polymorphisms (SNPs) and diabetes-associated traits were assessed.
Results: OCT3 mRNA and protein levels in SAT 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 to hip ratio, and circulating lipids (eg, triglycerides).
Conclusion: OCT3 mRNA and protein levels in SAT 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 in premenopausal vs postmenopausal women. High OCT3 protein levels in adipose tissue may result in increased catecholamine degradation, and this can contribute to the reduction in lipolysis observed in women with aging.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10690730 | PMC |
| http://dx.doi.org/10.1210/endocr/bqad172 | DOI Listing |
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