Estrogen normalizes maternal HFD-induced cardiac hypertrophy in offspring by regulating AT2R

in Journal of Endocrinology
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  • 1 Department of Pharmacology, Key Laboratory of Molecular Target & Clinical Pharmacology, School of, Pharmaceutical Sciences & the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, China
  • 2 Guangzhou Institute of Cardiovascular Disease, Guangzhou Key Laboratory of Cardiovascular Disease, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, China

Correspondence should be addressed to Q Xue or J Luo: xueqin1980@hotmail.com or jiandongluo@hotmail.com

*(F Chen and H Yu contributed equally to this work)

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Our previous study has demonstrated maternal high-fat diet (HFD) caused sex-dependent cardiac hypertrophy in adult male, but not female offspring. The present study tested the hypothesis that estrogen normalizes maternal HFD-induced cardiac hypertrophy by regulating angiotensin II receptor (ATR) expression in adult female offspring. Pregnant rats were divided into the normal diet (ND) and HFD (60% kcal fat) groups. Ovariectomy (OVX) and 17β-estradiol (E2) replacement were performed on 8-week-old female offspring. Maternal HFD had no effect on left ventricular (LV) wall thickness, cardiac function and molecular markers of cardiac hypertrophy function in sham groups. However, maternal HFD caused cardiac hypertrophy of offspring in OVX groups, which was abrogated by E2 replacement. In addition, maternal HFD had no effect on ERα and ERβ in sham groups. In contrast, HFD significantly decreased ERα, but not ERβ in OVX groups. In sham groups, there was no difference in the cardiac ATR type 1 (AT1R) and ATR type 2 (AT2R) between ND and HFD offspring. HFD significantly increased AT2R, but not AT1R in OVX groups. Furthermore, maternal HFD resulted in decreased glucocorticoid receptors (GRs) binding to the glucocorticoid response elements at the AT2R promoter, which was due to decreased GRs in hearts from OVX offspring. These HFD-induced changes in OVX groups were abrogated by E2 replacement. These results support a key role of estrogen in the sex difference of maternal HFD-induced cardiac hypertrophy in offspring, and suggest that estrogen protects female offspring from cardiac hypertrophy in adulthood by regulating AT2R.

 

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