N-acetylcysteine protects neonatal mice from ventricular hypertrophy induced by maternal obesity in a sex-specific manner

Zhang, Jialing; Cao, Li; Tan, Yanfeng; Zheng, Yuanzheng; Gui, Yonghao

doi:10.1016/j.biopha.2020.110989

Cited by 15 publications

(31 citation statements)

References 40 publications

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“…An additional nutritional supplement that has demonstrated a potential role in offspring cardiovascular health is N-acetyl cysteine (NAC) ( 89 ). Supplementation of NAC in diet of pregnant obese mice reduced ventricular hypertrophy in offspring.…”

Section: Nutritional Intervention In Animal Modelsmentioning

confidence: 99%

Maternal Obesity: A Focus on Maternal Interventions to Improve Health of Offspring

Shrestha

Prowak

Berlandi-Short

et al. 2021

Front. Cardiovasc. Med.

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Maternal obesity has many implications for offspring health that persist throughout their lifespan that include obesity and cardiovascular complications. Several different factors contribute to obesity and they encompass interplay between genetics and environment. In the prenatal period, untreated obesity establishes a foundation for a myriad of symptoms and negative delivery experiences, including gestational hypertensive disorders, gestational diabetes, macrosomia, and labor complications. However, data across human and animal studies show promise that nutritional interventions and physical activity may rescue much of the adverse effects of obesity on offspring metabolic health. Further, these maternal interventions improve the health of the offspring by reducing weight gain, cardiovascular disorders, and improving glucose tolerance. Mechanisms from animal studies have also been proposed to elucidate the signaling pathways that regulate inflammation, lipid metabolism, and oxidative capacity of the tissue, ultimately providing potential specific courses of treatment. This review aims to pinpoint the risks of maternal obesity and provide plausible intervention strategies. We delve into recent research involving both animal and human studies with maternal interventions. With the increasing concerning of obesity rates witnessed in the United States, it is imperative to acknowledge the long-term effects posed on future generations and specifically modify maternal nutrition and care to mitigate these adverse outcomes.

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Section: Nutritional Intervention In Animal Modelsmentioning

confidence: 99%

Maternal Obesity: A Focus on Maternal Interventions to Improve Health of Offspring

Shrestha

Prowak

Berlandi-Short

et al. 2021

Front. Cardiovasc. Med.

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show abstract

“…In the offspring heart of an obesity model with hyperglycemia and hyperinsulinemia, Zhang et al found that the mTORC1 signaling pathway was increased. These authors also found that a maternal treatment with the antioxidant N-acetyl-cysteine during pregnancy normalized the altered mTOR signaling in the offspring heart ( Zhang et al, 2021 ).…”

Section: Animal Studiesmentioning

confidence: 91%

“…In the male offspring heart from a mouse model of obesity and diabetes, Zhang et al found an increased expression of TGFβ-1 together with myocardial fibrosis and left ventricular structural alterations. These authors also found that all these programmed alterations were prevented by a maternal treatment with N-acetyl-cysteine during pregnancy (Zhang et al, 2021). Several downstream actions of TGF-β1 can be mediated by connective tissue growth factor (CTGF), a secreted multifunctional protein also involved in the regulation of ECM deposition during development as well as during pathological conditions (Frangogiannis, 2012).…”

Section: Animal Studies Focused On Alterations In the Cardiac Extracellular Matrix And Intercellular Communicationmentioning

confidence: 94%

“…In a study performed in a rat model of diabetes in pregnancy induced by STZ administration on day 12 of gestation, the heart of the 6-week-old offspring showed an increase in NOX1 and NOX2 together with an increase in reactive oxygen species in the left ventricle ( Chen et al, 2019 ), and the heart of adult offspring still showed an increase in NOX2 expression ( Zhang et al, 2018 ). Maternal treatment with N-acetyl-cysteine prevents the increased NOX2 transcript levels in the offspring heart from a model of obesity and diabetes ( Zhang et al, 2021 ).…”

Section: Animal Studiesmentioning

confidence: 99%

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Intrauterine Programming of Cardiovascular Diseases in Maternal Diabetes

2021

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Maternal diabetes is a prevalent pathology that increases the risk of cardiovascular diseases in the offspring, the heart being one of the main target organs affected from the fetal stage until the adult life. Metabolic, pro-oxidant, and proinflammatory alterations in the fetal heart constitute the first steps in the adverse fetal programming of cardiovascular disease in the context of maternal diabetes. This review discusses both human and experimental studies addressing putative mechanisms involved in this fetal programming of heart damage in maternal diabetes. These include cardiac epigenetic changes, alterations in cardiac carbohydrate and lipid metabolism, damaging effects caused by a pro-oxidant and proinflammatory environment, alterations in the cardiac extracellular matrix remodeling, and specific signaling pathways. Putative actions to prevent cardiovascular impairments in the offspring of mothers with diabetes are also discussed.

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“…Research has indicated that bioactive interventions in rodent models of maternal obesity could prevent adverse effects of maternal obesity and improve metabolic health of the offspring. Few bioactive interventions with positive effects in rodents include fish oil (FO), prebiotics and N acetyl cysteine [11][12][13][14]. This study focuses on fish and dietary FO supplements as they are prescribed during pregnancy [15].…”

Section: Introductionmentioning

confidence: 99%

Sex Differences in Early Programming by Maternal High Fat Diet Induced-Obesity and Fish Oil Supplementation in Mice

et al. 2021

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Pre-pregnancy obesity is a contributing factor for impairments in offspring metabolic health. Interventional strategies during pregnancy are a potential approach to alleviate and/or prevent obesity and obesity related metabolic alterations in the offspring. Fish oil (FO), rich in omega-3 polyunsaturated fatty acids (n-3 PUFAs) exerts metabolic health benefits. However, the role of FO in early life remains still unknown. Hence, this study objective was to determine the effect of FO supplementation in mice from pre-pregnancy through lactation, and to study the post-natal metabolic health effects in gonadal fat and liver of offspring fed high fat (HF) diet with or without FO. Female C57BL6J mice aged 4–5 weeks were fed a HF (45% fat) diet supplemented with or without FO (30 g/kg of diet) and low fat (LF; 10% fat) pre-pregnancy through lactation. After weaning, offspring (male and female) from HF or FO dams either continued the same diet (HF-HF and FO-FO) or switched to the other diet (HF-FO and FO-HF) for 13 weeks, creating four groups of treatment, and LF-LF was used as a control group. Serum, gonadal fat and liver tissue were collected at termination for metabolic analyses. Offspring of both sexes fed HF with or without fish oil gained (p < 0.05) more weight post weaning, compared to LF-LF-fed mice. All the female offspring groups supplemented with FO had reduced body weight compared to the respective male groups. Further, FO-FO supplementation in both sexes (p < 0.05) improved glucose clearance and insulin sensitivity compared to HF-HF. All FO-FO fed mice had significantly reduced adipocyte size compared to HF-HF group in both male and females. Inflammation, measured by mRNA levels of monocyte chemoattractant protein 1 (Mcp1), was reduced (p < 0.05) with FO supplementation in both sexes in gonadal fat and in the liver. Markers of fatty acid synthesis, fatty acid synthase (Fasn) showed no sex specific differences in gonadal fat and liver of mice supplemented with HF. Female mice had lower liver triglycerides than male counterparts. Supplementation of FO in mice improved metabolic health of offspring by lowering markers of lipid synthesis and inflammation.

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N-acetylcysteine protects neonatal mice from ventricular hypertrophy induced by maternal obesity in a sex-specific manner

Cited by 15 publications

References 40 publications

Maternal Obesity: A Focus on Maternal Interventions to Improve Health of Offspring

Maternal Obesity: A Focus on Maternal Interventions to Improve Health of Offspring

Intrauterine Programming of Cardiovascular Diseases in Maternal Diabetes

Sex Differences in Early Programming by Maternal High Fat Diet Induced-Obesity and Fish Oil Supplementation in Mice

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