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

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.

Data availability

Sequencing data have been deposited in GEO under accession code GSE162185 and a secure token for reviewers has been generated: cduxsaskdtkpxqb. All lipidomics data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for Figures 2, 3, 4 and 6.

The following data sets were generated

Article and author information

Author details

  1. Lucas C Pantaleao

    Metabolic Research Laboratories and MRC Metabolic Diseases Unit, University of Cambridge, Cambridge, United Kingdom
    For correspondence
    lp435@medschl.cam.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5626-8810
  2. Isabella Inzani

    Metabolic Research Laboratories and MRC Metabolic Diseases Unit, University of Cambridge, Cambridge, United Kingdom
    For correspondence
    ii233@medschl.cam.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
  3. Samuel Furse

    Metabolic Research Laboratories and MRC Metabolic Diseases Unit, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4267-2051
  4. Elena Loche

    Metabolic Research Laboratories and MRC Metabolic Diseases Unit, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0597-4520
  5. Antonia Hufnagel

    Metabolic Research Laboratories and MRC Metabolic Diseases Unit, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7030-4419
  6. Thomas Ashmore

    Metabolic Research Laboratories and MRC Metabolic Diseases Unit, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  7. Heather L Blackmore

    Metabolic Research Laboratories and MRC Metabolic Diseases Unit, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  8. Benjamin Jenkins

    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, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  9. Asha AM Carpenter

    Metabolic Research Laboratories and MRC Metabolic Diseases Unit, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  10. Ania Wilczynska

    Cancer Research UK Beatson Institute, Bearsden, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  11. Martin Bushell

    Cancer Research UK Beatson Institute, Bearsden, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  12. Albert Koulman

    Metabolic Research Laboratories and MRC Metabolic Diseases Unit, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  13. Denise S Fernandez-Twinn

    Metabolic Research Laboratories and MRC Metabolic Diseases Unit, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2610-277X
  14. Susan E Ozanne

    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, University of Cambridge, Cambridge, United Kingdom
    For correspondence
    seo10@cam.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8753-5144

Funding

British Heart Foundation (RG/17/12/33167)

  • Susan E Ozanne

Medical Research Council (MRC_MC_UU_00014/4)

  • Denise S Fernandez-Twinn

Wellcome Trust (208363/Z/17/Z)

  • Susan E Ozanne

British Heart Foundation (FS/12/64/30001)

  • Elena Loche

British Heart Foundation (FS/18/56/35177)

  • Isabella Inzani

Biotechnology and Biological Sciences Research Council (BB/M027252/1)

  • Samuel Furse

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: This research was regulated under the Animals (Scientific Procedures) Act 1986 Amendment Regulations 2012 following ethical review by the University of Cambridge Animal Welfare and Ethical Review Body (AWERB). The work carried out is approved under project licences number 80/2512 and P5FDF0206.

Reviewing Editor

  1. Arduino A Mangoni, Flinders Medical Centre, Australia

Publication history

  1. Received: April 3, 2021
  2. Preprint posted: April 12, 2021 (view preprint)
  3. Accepted: January 12, 2022
  4. Accepted Manuscript published: January 13, 2022 (version 1)
  5. Accepted Manuscript updated: January 18, 2022 (version 2)
  6. Version of Record published: January 27, 2022 (version 3)

Copyright

© 2022, Pantaleao et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Lucas C Pantaleao
  2. Isabella Inzani
  3. Samuel Furse
  4. Elena Loche
  5. Antonia Hufnagel
  6. Thomas Ashmore
  7. Heather L Blackmore
  8. Benjamin Jenkins
  9. Asha AM Carpenter
  10. Ania Wilczynska
  11. Martin Bushell
  12. Albert Koulman
  13. Denise S Fernandez-Twinn
  14. Susan E Ozanne
(2022)
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
eLife 11:e69078.
https://doi.org/10.7554/eLife.69078

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