Sex-dependent metabolic effects of maternal obesity on subcutaneous and visceral adipose tissue in offspring fed obesogenic diet after weaning.

Obesity and associated metabolic dysfunctions represent a major health problem worldwide.The prevalence of overweight and obesity among children has drastically increased during the last decades and maternal obesity has been demonstrated as an ultimate factor. Nutrition-stimulated transgenerational epigenetic regulation of key metabolic genes is fundamental to the developmental origins of the metabolic syndrome. A number of recent studies have suggested that fetal nutrition may differently influence male and female offspring, in both humans and mice. In this work, we investigated the sex-dependent programming effect of maternal obesity during preconception, conception and lactation periods in F1 offspring. Four-week old virgin C57Bl/6J female mice were randomly assigned for either the control diet or the high-fat diet for 6 weeks before mating and during gestation and lactation. All offspring were fed with the high-fat diet for the following 25 weeks until sacrifice. Magnetic resonance imaging and spectroscopy of adipose revealed that females had more total fat depot on body weight than males, in both mother diet groups. At early age, females had less visceral adipose tissue (VAT) than males and more subcutaneous adipose tissue (SAT) on total fat. In vivo magnetic resonance spectroscopy in adipose tissue, revealed that lipid composition varies between adipose depots and sexes. Bulk-RNA sequencing analysis of VAT and SAT revealed important reprogramming of gene expression in male SAT born from obese mothers compared to those from lean mothers. Our results demonstrated for the first time that sex-dependent gene programming exists in VAT and SAT and that, maternal obesity differentially reprogrammed the gene expression between VAT and SAT in females and males, which may contribute to the adverse metabolic responses to maternal obesity.