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Increased OCT3 Expression in Adipose Tissue With Aging: Implications for Catecholamine and Lipid Turnover and Insulin

Fozia Ahmed1, Milica Vranic1, Susanne Hetty1

  • 1Department of Medical Sciences, Clinical Diabetology and Metabolism, Uppsala University, 751 85 Uppsala, Sweden.

Endocrinology
|November 16, 2023
PubMed
Abstract

Insights

Organic cation transporter 3 (OCT3) levels in women's fat tissue increase with age, potentially worsening insulin resistance. Higher OCT3 may reduce fat breakdown, contributing to age-related adiposity.

Area of Science:

  • Endocrinology
  • Metabolism
  • Molecular Biology

Background:

  • Aging is associated with reduced catecholamine-stimulated lipolysis, potentially contributing to adiposity and insulin resistance.
  • Organic cation transporter 3 (OCT3) mediates catecholamine transport into adipocytes, and its inhibition by estradiol (E2) affects lipolysis.
  • The role of OCT3 in age-related metabolic changes in women requires further investigation.

Purpose of the Study:

  • To investigate the association of OCT3 mRNA levels in subcutaneous adipose tissue (SAT) with aging and insulin resistance markers in women.
  • To examine the effect of estradiol (E2) on OCT3 mRNA levels in SAT.
  • To assess the relationship between OCT3 single nucleotide polymorphisms (SNPs) and diabetes-associated traits.

Main Methods:

  • Subcutaneous adipose tissue (SAT) biopsies were collected from 66 women (aged 22-76 years) with or without type 2 diabetes.
  • OCT3 mRNA and protein levels were quantified and correlated with aging, insulin resistance markers, and ex vivo lipolysis.
  • SAT was incubated with E2 to assess its effect on OCT3 mRNA levels, and OCT3 SNPs were analyzed for associations with metabolic traits.

Main Results:

  • OCT3 mRNA and protein levels in SAT increased with aging and were higher in postmenopausal compared to premenopausal women.
  • Estradiol (E2) treatment dose-dependently reduced OCT3 mRNA levels in SAT.
  • OCT3 mRNA levels were negatively associated with insulin resistance markers and ex vivo lipolysis, while OCT3 SNPs correlated with BMI, waist-to-hip ratio, and triglyceride levels.

Conclusions:

  • OCT3 mRNA and protein levels in SAT increase with aging and are inversely related to insulin resistance markers in women.
  • Estradiol (E2) downregulates OCT3 mRNA, potentially explaining lower levels in premenopausal women.
  • Elevated OCT3 in adipose tissue may increase catecholamine degradation, contributing to reduced lipolysis and increased adiposity with aging.
Keywords:
OCT3T2Dadipose tissueagingestradiol

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