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Article

Promoting Glutathione Synthesis: A Possibility for Treating Cardiomyopathy Induced by a Maternal Western Diet

1
Institute of Pediatrics, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai 201102, China
2
National Health Commission (NHC) Key Laboratory of Neonatal Diseases, Fudan University, Shanghai 201102, China
3
Cardiovascular Center, Children’s Hospital of Fudan University, Shanghai 201102, China
4
Ultrasound Department, Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200090, China
*
Authors to whom correspondence should be addressed.
Nutrients 2024, 16(15), 2520; https://doi.org/10.3390/nu16152520
Submission received: 5 June 2024 / Revised: 30 July 2024 / Accepted: 30 July 2024 / Published: 1 August 2024
(This article belongs to the Section Nutrition and Metabolism)

Abstract

Background: The adverse effects of a Western diet on obesity and diabetes among reproductive-aged women pose a significant threat to the cardiovascular health of their offspring. Given the crucial role of glutathione metabolism and glutathione-related antioxidant defense systems in cardiovascular diseases through scavenging ROS and maintaining redox homeostasis, further exploration of their specific influence is imperative to develop therapeutic strategies for cardiomyopathy induced by a maternal Western diet. Methods: We developed a prenatal maternal Western diet exposure model in C57/B6 mice to investigate cardiac morphology and function through histological analysis and echocardiography. RNA sequencing and analysis were utilized to elucidate the mechanisms underlying the impact of a maternal Western diet and N-acetylcysteine treatment on cardiomyopathy. Additionally, ELISAs, transmission electron microscopy, and flow cytometry were employed to assess the antioxidant defense system and mitochondrial ROS levels in progenitor cardiomyocytes. Results: N-acetylcysteine significantly mitigated cardiomyocyte hypertrophy, myocardial interstitial fibrosis, collagen type I accumulation, and left ventricular remodeling induced by a maternal Western diet, particularly in male offspring. Furthermore, N-acetylcysteine reversed the increase in apoptosis and the increase in the β/α-MyHC ratio in the myocardium of offspring that results from a maternal Western diet. RNA sequencing and GSEA revealed that the beneficial effects of N-acetylcysteine were linked to its ability to modulate oxidative phosphorylation pathways. Additionally, N-acetylcysteine treatment during pregnancy can markedly elevate glutathione levels, augment glutathione peroxidase (GPx) activity, and mitigate the accumulation of mitochondrial ROS caused by a maternal Western diet. Conclusions: N-acetylcysteine mitigated cardiomyopathy induced by a maternal Western diet by bolstering glutathione synthesis and enhancing GPx activity, thereby scavenging mitochondrial ROS and modulating oxidative phosphorylation pathways.
Keywords: cardiomyopathy; developmental origins of disease; glutathione; reactive oxygen species; oxidative phosphorylation cardiomyopathy; developmental origins of disease; glutathione; reactive oxygen species; oxidative phosphorylation

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MDPI and ACS Style

Zhang, J.; Wang, J.; Xu, D.; Gui, Y.; Bai, F.; Huo, Y.; Cao, L.; Gui, Y. Promoting Glutathione Synthesis: A Possibility for Treating Cardiomyopathy Induced by a Maternal Western Diet. Nutrients 2024, 16, 2520. https://doi.org/10.3390/nu16152520

AMA Style

Zhang J, Wang J, Xu D, Gui Y, Bai F, Huo Y, Cao L, Gui Y. Promoting Glutathione Synthesis: A Possibility for Treating Cardiomyopathy Induced by a Maternal Western Diet. Nutrients. 2024; 16(15):2520. https://doi.org/10.3390/nu16152520

Chicago/Turabian Style

Zhang, Jialing, Jiayu Wang, Da Xu, Yiting Gui, Fan Bai, Yu Huo, Li Cao, and Yonghao Gui. 2024. "Promoting Glutathione Synthesis: A Possibility for Treating Cardiomyopathy Induced by a Maternal Western Diet" Nutrients 16, no. 15: 2520. https://doi.org/10.3390/nu16152520

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