Sex-specific hepatic lipidic modulation in offspring born from obese mother contributes to the sexual dimorphism in the metabolic adaptation later in life

With the increasing prevalence of obesity in women of reproductive age, there is an urgent need to understand the metabolic impact on the fetus. Sex-related susceptibility to liver diseases has been demonstrated but the underlying mechanism safeguarding lipid homeostasis remains unclear. Here we report that maternal high fat diet (HFD) impacted whole body metabolism differently in female and male offspring. Males, but not females, gained more weight and showed impaired insulin sensitivity when born from mothers on HFD but not control diet. Although lipid mass was similar in the livers of offsprings born from HFD mothers, we detected sex-specific changes in the hepatic lipidome. We discovered sex-specific modifications in the composition of fatty acid, triglyceride and the phospholipid. These overall changes could be linked to sex-specific regulation of genes controlling metabolic pathways. Our findings revised the current assumption that sex-dependent susceptibility to metabolic disorders is caused by sex-specific postnatal regulation and instead provided molecular evidence supporting in utero metabolic adaptations in the offspring of obese mothers.