{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T12:21:23Z","timestamp":1772799683105,"version":"3.50.1"},"reference-count":53,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2024,8,1]],"date-time":"2024-08-01T00:00:00Z","timestamp":1722470400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Shanghai High-Level Local University Construction Project\u2014First-class Clinical Medicine Discipline Development Project\u2014Child Development and Health","award":["DGF501062"],"award-info":[{"award-number":["DGF501062"]}]},{"name":"Shanghai High-Level Local University Construction Project\u2014First-class Clinical Medicine Discipline Development Project\u2014Child Development and Health","award":["IDF156014"],"award-info":[{"award-number":["IDF156014"]}]},{"name":"Fudan University\u2019s Key Project for Double First-class Construction of Disciplines, Early Childhood Healthy Development and Maintenance","award":["DGF501062"],"award-info":[{"award-number":["DGF501062"]}]},{"name":"Fudan University\u2019s Key Project for Double First-class Construction of Disciplines, Early Childhood Healthy Development and Maintenance","award":["IDF156014"],"award-info":[{"award-number":["IDF156014"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>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 \u03b2\/\u03b1-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.<\/jats:p>","DOI":"10.3390\/nu16152520","type":"journal-article","created":{"date-parts":[[2024,8,1]],"date-time":"2024-08-01T18:04:59Z","timestamp":1722535499000},"page":"2520","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Promoting Glutathione Synthesis: A Possibility for Treating Cardiomyopathy Induced by a Maternal Western Diet"],"prefix":"10.3390","volume":"16","author":[{"given":"Jialing","family":"Zhang","sequence":"first","affiliation":[{"name":"Institute of Pediatrics, Children\u2019s Hospital of Fudan University, National Children\u2019s Medical Center, Shanghai 201102, China"},{"name":"National Health Commission (NHC) Key Laboratory of Neonatal Diseases, Fudan University, Shanghai 201102, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5608-0738","authenticated-orcid":false,"given":"Jiayu","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Pediatrics, Children\u2019s Hospital of Fudan University, National Children\u2019s Medical Center, Shanghai 201102, China"},{"name":"National Health Commission (NHC) Key Laboratory of Neonatal Diseases, Fudan University, Shanghai 201102, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Da","family":"Xu","sequence":"additional","affiliation":[{"name":"National Health Commission (NHC) Key Laboratory of Neonatal Diseases, Fudan University, Shanghai 201102, China"},{"name":"Cardiovascular Center, Children\u2019s Hospital of Fudan University, Shanghai 201102, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yiting","family":"Gui","sequence":"additional","affiliation":[{"name":"National Health Commission (NHC) Key Laboratory of Neonatal Diseases, Fudan University, Shanghai 201102, China"},{"name":"Cardiovascular Center, Children\u2019s Hospital of Fudan University, Shanghai 201102, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fan","family":"Bai","sequence":"additional","affiliation":[{"name":"National Health Commission (NHC) Key Laboratory of Neonatal Diseases, Fudan University, Shanghai 201102, China"},{"name":"Cardiovascular Center, Children\u2019s Hospital of Fudan University, Shanghai 201102, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Huo","sequence":"additional","affiliation":[{"name":"National Health Commission (NHC) Key Laboratory of Neonatal Diseases, Fudan University, Shanghai 201102, China"},{"name":"Cardiovascular Center, Children\u2019s Hospital of Fudan University, Shanghai 201102, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3391-0513","authenticated-orcid":false,"given":"Li","family":"Cao","sequence":"additional","affiliation":[{"name":"Ultrasound Department, Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200090, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9414-4448","authenticated-orcid":false,"given":"Yonghao","family":"Gui","sequence":"additional","affiliation":[{"name":"National Health Commission (NHC) Key Laboratory of Neonatal Diseases, Fudan University, Shanghai 201102, China"},{"name":"Cardiovascular Center, Children\u2019s Hospital of Fudan University, Shanghai 201102, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2000","DOI":"10.1001\/jama.2023.19897","article-title":"Obesity Management in Adults: A Review","volume":"330","author":"Schwartz","year":"2023","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1007\/s00125-022-05851-x","article-title":"Empagliflozin protects mice against diet-induced obesity, insulin resistance and hepatic steatosis","volume":"66","author":"Radlinger","year":"2023","journal-title":"Diabetologia"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1842","DOI":"10.1016\/S0140-6736(18)30312-X","article-title":"Origins of lifetime health around the time of conception: Causes and 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