Related Experiment Video

Updated: Sep 23, 2025

An In Vivo Estrogen Deficiency Mouse Model for Screening Exogenous Estrogen Treatments of Cardiovascular Dysfunction After Menopause
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An In Vivo Estrogen Deficiency Mouse Model for Screening Exogenous Estrogen Treatments of Cardiovascular Dysfunction After Menopause

Published on: August 13, 2019

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Estrogen Protects Cardiac Function and Energy Metabolism in Dilated Cardiomyopathy Induced by Loss of Cardiac IRS1

Hui Yan1,2, Wanbao Yang1, Fenghua Zhou1

  • 1Department of Nutrition, College of Agriculture and Life Sciences (H.Y., W.Y., F.Z., Q.P., K.A., C.A., Y.S., S.G.), Texas A&M University, College Station.

Circulation. Heart Failure
|May 17, 2022
PubMed
Abstract

Insights

Estrogen protects against cardiac insulin resistance and diabetic cardiomyopathy in mice. This finding may explain gender differences in type 2 diabetes and cardiovascular disease incidence.

Area of Science:

  • Cardiovascular Research
  • Endocrinology
  • Metabolic Diseases

Background:

  • Type 2 diabetes (T2D) increases cardiovascular disease (CVD) risk.
  • Gender disparities in T2D and CVD incidence emerge postmenopause, suggesting a protective role for ovarian hormones like estrogen.
  • Cardiac insulin resistance is a key factor in developing diabetic cardiomyopathy.

Purpose of the Study:

  • To investigate the protective role of ovaries and estrogen in cardiac function and energy metabolism.
  • To utilize cardiac insulin receptor substrate (IRS) 1 and IRS2 double gene knockout mice to model cardiac insulin resistance.

Main Methods:

  • Mice with heart-specific IRS1/2 gene knockout were treated with placebo or 17β-estradiol (E2).
  • Female mice underwent ovariectomy to remove endogenous E2.
  • Cardiac function and energy metabolism were assessed via echocardiography and indirect calorimetry.

Main Results:

  • Estrogen supplementation (E2) prevented dilated cardiomyopathy and improved cardiac function and energy metabolism in mice with cardiac IRS1/2 deficiency.
  • E2 enhanced lifespan in both male and ovariectomized female mice with genetic cardiac insulin resistance.
  • These benefits were linked to the activation of Akt-Foxo1 signaling pathways.

Conclusions:

  • Estrogen confers protection against diabetic cardiomyopathy induced by cardiac insulin resistance.
  • This mechanism may underlie gender-based differences in T2D and CVD incidence.
  • Estrogen signaling represents a potential therapeutic target for improving cardiac function and metabolism in T2D patients.
Keywords:
diabetic cardiomyopathyenergy metabolismestradiolestrogeninsulin resistance

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