Pre-conceptional maternal metabolic status influences hepatic metabolome in male offspring

Background/Aims Maternal obesity is associated with fertility disorders, obstetric complications, and development of metabolic syndrome in offspring. The recommendation to overweight or obese women is to lose weight before pregnancy, but the impact of these prescriptions on the offspring health is insufficiently studied. Previous results on late-term mice fetuses have shown that maternal obesity leads to fetal growth restriction and to the modification of epigenetic machinery-related gene expression in fetal liver and placenta. Moreover, fetuses from the preconceptional weight loss maternal group normalize their growth, but some fetal genes stay differentially expressed. Method We analysed the metabolic phenotype of offspring born to control (CTRL), obese (OB) or weight loss after diet-induced obesity (WL) mothers. To highlight a possible conditioning effect, offspring were either fed a control (CD) or a high fat diet (HFD). Their metabolism and olfactory behavior were monitored for up to 6 months. Then, we analyzed the metabolome of three tissues involved in food intake and nutrient management (liver, olfactory bulb and hypothalamus) in male adult offspring. Results Multiple Factorial Analysis integration of offspring phenotypic data showed a major influence of the post-weaning diet and pointed a difference in HFD-fed males according to their maternal group (OB vs WL). This confirmed a sex-dependant metabolic conditioning by the maternal environment. The olfactory sensitivity, measured by electro-olfactogram, was reduced in WL male offspring, whatever the postnatal diet. The metabolomics study annotated 278, 258 and 200 metabolites in the liver, olfactory bulb and hypothalamus respectively. Again, the post-weaning diet had a major effect in the three tissues but interestingly, the maternal group also influenced the hepatic metabolome of adult offspring. Conclusions These data, integrating metabolism, olfactory behavior and metabolome, provide new and original information on the effects of preconceptional maternal metabolic status in the offspring health conditioning upon diet challenges