Maternal diet-induced obesity during pregnancy alters lipid supply to mouse E18.5 fetuses and changes the cardiac tissue lipidome in a sex-dependent manner

  1. Lucas C Pantaleão
  2. Isabella Inzani
  3. Samuel Furse
  4. Elena Loche
  5. Antonia Hufnagel
  6. Thomas Ashmore
  7. Heather L Blackmore
  8. Benjamin Jenkins
  9. Asha A M Carpenter
  10. Ania Wilczynska
  11. Martin Bushell
  12. Albert Koulman
  13. Denise S Fernandez-Twinn
  14. Susan E Ozanne

  • Curated by eLife

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    Evaluation Summary:

    This manuscript describes the effects of maternal diet-induced obesity on lipid composition in maternal and fetal serum and the fetal heart, and in the fetal heart transcriptome. This study revealed sex-specific effects of obesity during pregnancy. The results presented provide insight into the still poorly understood processes influencing the long-term health of the fetus.

    (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

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Abstract

Maternal obesity during pregnancy has immediate and long-term detrimental effects on the offspring heart. In this study, we characterized the cardiac and circulatory lipid profiles in late gestation E18.5 fetuses of diet-induced obese pregnant mice and established the changes in lipid abundance and fetal cardiac transcriptomics. We used untargeted and targeted lipidomics and transcriptomics to define changes in the serum and cardiac lipid composition and fatty acid metabolism in male and female fetuses. From these analyses we observed: (1) maternal obesity affects the maternal and fetal serum lipidome distinctly; (2) female fetal heart lipidomes are more sensitive to maternal obesity than males; (3) changes in lipid supply might contribute to early expression of lipolytic genes in mouse hearts exposed to maternal obesity. These results highlight the existence of sexually dimorphic responses of the fetal heart to the same in utero obesogenic environment and identify lipids species that might mediate programming of cardiovascular health.

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  1. Version published to 10.7554/elife.69078 on eLife
  2. eLife

    Reviewer 2 (Public review):

    In this study the authors investigated the effects of maternal obesity on plasma lipid, the cardiac transcriptome and lipidomics in the maternal and fetal mouse heart. Their major conclusions were that maternal obesity has different effects on the maternal and fetal lipidome; the changes are greater in the fetal female heart than the fetal male showing sexual dimorphism in programming and that changes in the transcriptome may reflect alterations in lipids. The study is well conducted and will add significantly to the literature on developmental programming by maternal obesity.

    The authors use a well-established model. The methods are all state of the art. I find no problems with any of the data. Maternal obesity is now an epidemic with consequences for mother and fetus. Thus this study is timely and will be valuable in assessing potential interventions and management strategies for the offspring of obese mothers.

  3. eLife

    Reviewer 1 (Public Review):

    The manuscript by Pantaleao et. al., describes the effects of maternal diet-induced obesity on lipid composition in maternal and fetal serum and the fetal heart, and in the fetal heart transcriptome. Lipid composition in fetal serum and heart was analyzed in males and females. This study revealed sex-specific effects of obesity during pregnancy. The authors found changes in the lipidome of both mother and fetus in response to obesity. Many of the lipid profiles exhibit sex specific changes in the fetal sera. Similarly, the authors identified sex-specific changes to the lipidome of the fetal heart. Through the use of transcriptomic analysis on the fetal heart, the authors identified changes in the expression of genes regulating lipid metabolism. The results presented provide insight into the still poorly understood processes influencing the long-term health of the fetus.

    The work characterizes an important aspect of the effects of maternal obesity and the results are visually well presented. A limitation is that this is a largely descriptive study. Nonetheless, the authors provide a detailed description of the lipid composition changes in response to maternal obesity and associated with sex.

    The introduction provides key information about the effects of obesity during pregnancy in the offspring, and the relevance of lipids in heart homeostasis. However, cardiac transcriptional regulation and sex-specific responses, which are the other key components of this study, could be more cohesively integrated.

    Some of the results presented can be analyzed in deeper detail to establish correlation between sex and diet with lipid composition and cardiac gene expression.

  4. eLife

    Evaluation Summary:

    This manuscript describes the effects of maternal diet-induced obesity on lipid composition in maternal and fetal serum and the fetal heart, and in the fetal heart transcriptome. This study revealed sex-specific effects of obesity during pregnancy. The results presented provide insight into the still poorly understood processes influencing the long-term health of the fetus.

    (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

  5. Version published to 10.1101/2021.04.12.439435v1 on bioRxiv