Estradiol-mediated improvements in adipose tissue insulin sensitivity are related to the balance of adipose tissue estrogen receptor α and β in postmenopausal women.
Level 2 - randomized trial
Individual randomized crossover trial
PubMed 28472101 · doi:10.1371/journal.pone.0176446
What was done
In a randomized crossover trial, 35 postmenopausal women (16 early postmenopausal, ≤6 years past menopause; 19 late postmenopausal, ≥10 years past menopause) received 1 week of transdermal estradiol (E2) or placebo. Subcutaneous adipose tissue (SAT) biopsies were collected in the fasted state after each intervention and analyzed for nuclear and cytosolic ERα and ERβ protein content (Western blot) and ESR1 mRNA expression (qPCR).
What was found
ESR1 mRNA expression increased ~1.4-fold after E2 treatment in both groups, but ERα and ERβ total protein expression did not differ between groups at baseline or post-treatment. The ratio of ERα to ERβ protein in the SAT nuclear fraction increased 10% in early postmenopausal women but decreased 25% in late postmenopausal women (group x treatment interaction, p<0.05). A higher baseline nuclear ERα/ERβ ratio was correlated with greater improvement in adipose tissue insulin sensitivity (lipolysis suppression EC50) following E2 treatment (r = -0.431, p<0.05).
Why it matters
These findings suggest that the subcellular balance of ERα and ERβ in subcutaneous fat, rather than absolute receptor levels, mediates estradiol's beneficial effects on adipose tissue insulin sensitivity after menopause.
Limits
The study had a small sample size (n = 35) and assessed only short-term (1-week) transdermal treatment. Only subcutaneous fat was evaluated, leaving effects in visceral depots unmeasured.
Cited by
- context Excessively high estradiol levels suppress lipolysis and promote insulin resistance and energy storage.