Obese mother offspring have hepatic lipidic modulation that contributes to sex-dependent metabolic adaptation later in life

Christina Savva,Marcela González-Granillo,Marion Korach-André,Bo Angelin,Claudia Kutter,Luisa A Helguero,Tânia Melo,Daniela Couto,Maria Rosário Domingues,Xidan Li

doi:10.1038/s42003-020-01513-z

Abstract

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 remains unclear. Here we report that maternal obesity impacts lipid metabolism differently in female and male offspring. Males, but not females, gained more weight and had impaired insulin sensitivity when born from obese mothers compared to control. Although lipid mass was similar in the livers of female and male offspring, sex-specific modifications in the composition of fatty acids, triglycerides and phospholipids was observed. 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 we provide molecular evidence supporting in utero metabolic adaptations in the offspring of obese mothers.

Highlights

With the increasing prevalence of obesity in women of reproductive age, there is an urgent need to understand the metabolic impact on the fetus
Our findings show that metabolic adaptation to Maternal obesity (MO) in the offspring is sex-dependent due to sex-specific transcriptional and post-transcriptional regulation of genes involved in lipid metabolism
We refer to offspring born from high-fat diet (HFD) mothers as HF/C and those born from control diet (CD) mothers as C/C (Fig. 1a)

Summary

Introduction

With the increasing prevalence of obesity in women of reproductive age, there is an urgent need to understand the metabolic impact on the fetus. Lipid mass was similar in the livers of female and male offspring, sex-specific modifications in the composition of fatty acids, triglycerides and phospholipids was observed. These overall changes could be linked to sexspecific regulation of genes controlling metabolic pathways. Closer inspection revealed an estrogen-dependent regulation of key genes in lipid pathways, which may explain the sex-specific metabolic responses in the offspring later in life[5,11,14,15]. Even though recent studies have shown intriguing sex differences in the metabolic response to obesity, both in human[16] and rodent models[11,17,18], sex-dependent adaptation to high-calorie intake is still unclear. Primarily addressing the effects in liver, these consequences may compromise the functions of other organs

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Conclusion