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

Author:

Pantaleão Lucas C1ORCID,Inzani Isabella1ORCID,Furse Samuel12ORCID,Loche Elena1ORCID,Hufnagel Antonia1ORCID,Ashmore Thomas1,Blackmore Heather L1,Jenkins Benjamin12,Carpenter Asha A M1,Wilczynska Ania34,Bushell Martin34ORCID,Koulman Albert12ORCID,Fernandez-Twinn Denise S1ORCID,Ozanne Susan E1ORCID

Affiliation:

1. Wellcome-MRC Institute of Metabolic Science and Medical Research Council Metabolic Diseases Unit, University of Cambridge, Addenbrooke’s Hospital

2. Core Metabolomics and Lipidomics Laboratory, Wellcome-MRC Institute of Metabolic Science, University of Cambridge, Addenbrooke’s Treatment Centre

3. Cancer Research UK Beatson Institute

4. Institute of Cancer Sciences, University of Glasgow

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.

Funder

British Heart Foundation

Medical Research Council

Wellcome Trust

Biotechnology and Biological Sciences Research Council

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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