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

Maternal obesity induces adverse cardiac programming in offspring, and effective interventions are needed to prevent cardiovascular ill-health. Herein we hypothesized that exposure to maternal obesogenic diet-induced obesity in mice results in left ventricular remodelling and hypertrophy in early childhood, and that maternal N-acetylcysteine (NAC) treatment alleviates these effects in a sex-dependent manner. The maternal obesity was induced in mice by the consumption of a Western diet accompanied by a 20 % sucrose solution. To determine the effect of NAC on the cardiac outcomes induced by maternal obesity, obese dams were continuously exposed to the obesogenic diet, with or without the oral NAC treatment during pregnancy. Left ventricular remodelling and hypertrophy occurred as early as 7 days after birth in the male offspring of obese dams (O-OB) compared with controls (O-CO). An over-expression of key genes and markers related to cardiac fibrosis accompanied by more disorganized myofibrils was observed in the hearts of neonatal male O-OB mice. When we next evaluated the level of oxidative stress in the hearts of neonatal mice, the activity of enzymatic antioxidants declined and expression of NOX enzyme complex was up-regulated in O-OB offspring hearts, but was normal in the offspring of NAC treated mice (O-OB/NAC). Maternal obesity also activated cardiac Akt and mammalian target of rapamycin (mTOR) signalling in offspring, and NAC treatment restored offspring cardiac Akt-mTOR signalling to normal irrespective of sex. NAC treatment did not prevent cardiomyocyte hypertrophy but did alleviate increased heart weight, interventricular septal thickness, and collagen content in male O-OB/NAC pups. Collectively, our results indicated that NAC blunted cardiac fibrosis and related ventricular hypertrophy of male neonatal offspring in the setting of maternal obesity, potentially acting by reducing oxidative stress. The present study provides a basis for investigating the role of NAC in nutrition-related cardiac programming.

Zhang J ，Cao L ，Tan Y ，Zheng Y ，Gui Y ... -  《-》

Maternal androgen excess induces cardiac hypertrophy and left ventricular dysfunction in female mice offspring.

Polycystic ovary syndrome (PCOS) is a common endocrinopathy that is suggested to increase the risk for cardiovascular disease. How PCOS may lead to adverse cardiac outcomes is unclear and here we hypothesized that prenatal exposure to dihydrotestosterone (DHT) and/or maternal obesity in mice induce adverse metabolic and cardiac programming in female offspring that resemble the reproductive features of the syndrome. The maternal obese PCOS phenotype was induced in mice by chronic high-fat-high-sucrose consumption together with prenatal DHT exposure. The prenatally androgenized (PNA) female offspring displayed cardiac hypertrophy during adulthood, an outcome that was not accompanied by aberrant metabolic profile. The expression of key genes involved in cardiac hypertrophy was up-regulated in the PNA offspring, with limited or no impact of maternal obesity. Furthermore, the activity of NADPH oxidase, a major source of reactive oxygen species in the cardiovascular system, was down-regulated in the PNA offspring heart. We next explored for early transcriptional changes in the heart of newly born PNA offspring, which could account for the long-lasting changes observed in adulthood. Neonatal PNA hearts displayed an up-regulation of transcription factors involved in cardiac hypertrophic remodelling and of the calcium-handling gene, Slc8a2. Finally, to determine the specific role of androgens in cardiovascular function, female mice were continuously exposed to DHT from pre-puberty to adulthood, with or without the antiandrogen flutamide. Continuous exposure to DHT led to adverse left ventricular remodelling, and increased vasocontractile responses, while treatment with flutamide partly alleviated these effects. Taken together, our results indicate that intrauterine androgen exposure programmes long-lasting heart remodelling in female mouse offspring that is linked to left ventricular hypertrophy and highlight the potential risk of developing cardiac dysfunction in daughters of mothers with PCOS.

Manti M ，Fornes R ，Pironti G ，McCann Haworth S ，Zhengbing Z ，Benrick A ，Carlström M ，Andersson D ，Stener-Victorin E ... -  《-》

Normalisation of circulating adiponectin levels in obese pregnant mice prevents cardiac dysfunction in adult offspring.

Vaughan OR ，Rosario FJ ，Powell TL ，Jansson T ... -  《-》

Maternal diet-induced obesity programmes cardiac dysfunction in male mice independently of post-weaning diet.

Loche E ，Blackmore HL ，Carpenter AA ，Beeson JH ，Pinnock A ，Ashmore TJ ，Aiken CE ，de Almeida-Faria J ，Schoonejans JM ，Giussani DA ，Fernandez-Twinn DS ，Ozanne SE ... -  《-》

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

Zhang J ，Wang J ，Xu D ，Gui Y ，Bai F ，Huo Y ，Cao L ，Gui Y ... -  《Nutrients》