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

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 17 beta-estradiol (E-2) 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 E-2 replacement. In addition, maternal HFD had no effect on ER alpha and ER beta in sham groups. In contrast, HFD significantly decreased ER alpha, but not ER beta in OVX groups. In sham groups, there was no difference in the cardiac ATR type 1 (AT(1)R) and ATR type 2 (AT(2)R) between ND and HFD offspring. HFD significantly increased AT(2)R, but not AT(1)R in OVX groups. Furthermore, maternal HFD resulted in decreased glucocorticoid receptors (GRs) binding to the glucocorticoid response elements at the AT(2)R promoter, which was due to decreased GRs in hearts from OVX offspring. These HFD-induced changes in OVX groups were abrogated by E-2 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 AT(2)R.

Automated summary

The study demonstrates that estrogen can protect female offspring from maternal high-fat diet-induced cardiac hypertrophy by regulating AT(2)R expression.