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

in Journal of Endocrinology
Authors:
Fangyuan Chen Department of Pharmacology, Key Laboratory of Molecular Target & Clinical Pharmacology, School of, Pharmaceutical Sciences & the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, China

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Haili Yu Department of Pharmacology, Key Laboratory of Molecular Target & Clinical Pharmacology, School of, Pharmaceutical Sciences & the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, China

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Haichuan Zhang Department of Pharmacology, Key Laboratory of Molecular Target & Clinical Pharmacology, School of, Pharmaceutical Sciences & the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, China

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Runzhu Zhao Department of Pharmacology, Key Laboratory of Molecular Target & Clinical Pharmacology, School of, Pharmaceutical Sciences & the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, China

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Kaifang Cao Department of Pharmacology, Key Laboratory of Molecular Target & Clinical Pharmacology, School of, Pharmaceutical Sciences & the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, China

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Yinghua Liu Department of Pharmacology, Key Laboratory of Molecular Target & Clinical Pharmacology, School of, Pharmaceutical Sciences & the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, China
Guangzhou Institute of Cardiovascular Disease, Guangzhou Key Laboratory of Cardiovascular Disease, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, China

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Jiandong Luo Department of Pharmacology, Key Laboratory of Molecular Target & Clinical Pharmacology, School of, Pharmaceutical Sciences & the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, China
Guangzhou Institute of Cardiovascular Disease, Guangzhou Key Laboratory of Cardiovascular Disease, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, China

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Qin Xue Department of Pharmacology, Key Laboratory of Molecular Target & Clinical Pharmacology, School of, Pharmaceutical Sciences & the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, China
Guangzhou Institute of Cardiovascular Disease, Guangzhou Key Laboratory of Cardiovascular Disease, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, China

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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)

DOI:
https://doi.org/10.1530/JOE-20-0562
Volume/Issue:
Volume 250: Issue 1
Article Type:
Research Article
Page Range:
1–12
Online Publication Date:
16 Jun 2021
Copyright:
© Society for Endocrinology 2021
Restricted access
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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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Print ISSN:
0022-0795
Online ISSN:
1479-6805
Copyright:
© Society for Endocrinology 2021
Page(s):
12
Article Type:
Research Article
Received Date:
23 Jan 2021
Accepted Date:
10 May 2021
Print Publication Date:
01 Jul 2021
Online Publication Date:
16 Jun 2021
Keywords:
estrogen; sex difference; maternal high-fat diet; angiotensin II receptors; glucocorticoid receptor

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