Antioxidant N-acetyl-cysteine administration in pregnant mice has long-term positive effects on metabolic and behavioural endpoints of male and female offspring prenatally exposed to a high-fat-diet

Consumption of a high-fat-diet (HFD) during pregnancy acts as powerful prenatal stressor leading to adult stress-related metabolic or behavioural disorders. We hypothesized that administration of antioxidants throughout gestation might counteract the negative effects of maternal HFD feeding during pregnancy on the developing foetus. Female C57BL/6J mice were fed HFD for 13 weeks and exposed to the N-acetyl-cysteine (NAC) antioxidant from 10-weeks of age until right before delivery. Body weight of the offspring was assessed from birth until adulthood. At this age, the metabolic, neuroendocrine and emotional profiles were also tested. Prenatal HFD increased mother and offspring body weight when administered in conjunction with NAC. In female offspring, NAC reduced the increase in leptin levels resulting from prenatal HFD. NAC administration resulted also in greater glucose tolerance, insulin sensitivity and increased adiponectin levels. Exploratory behaviour was increased in NAC offspring, an effect accompanied by reduced stress-induced plasma corticosterone levels. Moreover, prenatal HFD administration led to reduced glutathione levels in the hypothalamus of males while NAC was able to revert this effect both in the brain (males) as well as in the brown adipose tissue (both males and females). Overall, results from this study indicate that the body redox milieu should be tightly regulated during foetal life and that buffering oxidative stress during pregnancy can have important long-term consequences on metabolic and behavioural endpoints. Support: H2020 AwE (N. 633589).