Region-specific effects of oestradiol on adipose-derived stem cell differentiation in post-menopausal women.

Kimberly A Cox‐York,Rocio I Pereira,Daniel H Bessesen,Christopher B Erickson,Rachael E Van Pelt

doi:10.1111/jcmm.13011

Abstract

The goal of this study was to determine the effect of acute transdermal 17β‐oestradiol (E2) on the adipogenic potential of subcutaneous adipose‐derived stem cells (ASC) in post‐menopausal women. Post‐menopausal women (n = 11; mean age 57 ± 4.5 years) were treated for 2 weeks, in a randomized, cross‐over design, with transdermal E2 (0.15 mg) or placebo patches. Biopsies of abdominal (AB) and femoral (FEM) subcutaneous adipose tissue (SAT) were obtained after each treatment and mature adipocytes were analysed for cell size and ASC for their capacity for proliferation (growth rate), differentiation (triglyceride accumulation) and susceptibility to tumour necrosis factor alpha‐induced apoptosis. Gene expression of oestrogen receptors α and β (ESR1 and ESR2), perilipin 1 and hormone‐sensitive lipase (HSL), was also assessed. In FEM SAT, but not AB SAT, 2 weeks of E2 significantly (P = 0.03) increased ASC differentiation and whole SAT HSL mRNA expression (P = 0.03) compared to placebo. These changes were not associated with mRNA expression of oestrogen receptors α and β, but HSL expression was significantly increased in FEM SAT with transdermal E2 treatment. Adipose‐derived stem cells proliferation and apoptosis did not change in either SAT depot after E2 compared with placebo. Short‐term E2 appeared to increase the adipogenic potential of FEM, but not AB, SAT in post‐menopausal women with possible implications for metabolic disease. Future studies are needed to determine longer term impact of E2 on regional SAT accumulation in the context of positive energy imbalance.

Highlights

Loss of endogenous ovarian hormones is thought to play a role in menopause-related increases in subcutaneous adipose tissue (SAT) accumulation, shifts in SAT distribution from the femoral (FEM) to abdominal (AB) region
We previously reported that in post-menopausal women, acute E2 treatment resulted in decreased cell size and increased cell number in FEM, but not AB SAT [16]
We recently reported that pre-menopausal women have smaller adipocytes in FEM SAT than post-menopausal women, and that 2 weeks of E2 treatment in post-menopausal women resulted in a reduction in mean adipocyte size in FEM SAT [16]

Summary

Introduction

Loss of endogenous ovarian hormones is thought to play a role in menopause-related increases in subcutaneous adipose tissue (SAT) accumulation, shifts in SAT distribution from the femoral (FEM) to abdominal (AB) region. This gynoid-to-android redistribution is proposed to contribute to the rise in cardiometabolic disease risk observed in women at the time of menopause [1, 2]. Human ASC treated in vitro with E2 exhibited altered adipogenic potential [12, 13], and 3 months of E2 treatment altered the expression of genes central to lipogenesis (e.g. SCD1, FAS, ACC1) in SAT a 2016 The Authors

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