Obese mother offspring have modulated hepatic lipid responses that contribute to sex-dependent metabolic adaptation later in life

Recent studies have demonstrated that females and males differ significantly in their response to obesity-associated metabolic adaptation. Maternal obesity is key in the development of metabolic complications in offspring later in life. However, how maternal obesity impact on the fetus is still largely unknown. It this study, we investigated the sex-dependent response to maternal obesity in obese offspring with a special focus on liver diseases. Here, we report that maternal obesity prior and during gestation in mice led to insulin resistance in male offspring and protect female offspring from developing hepatocellular carcinoma. We found that females but not males born from obese mother reprogram metabolic pathways to better prevent the damaging impact of maternal obesity on offspring health later in life. Our findings reveal that maternal obesity impact differently female and male offspring by reprogramming transcriptional and posttranscriptional activity in a sex-dependent manner.