Maternal obesity causes fetal cardiac hypertrophy and alters adult offspring myocardial metabolism in mice

Vaughan, O. R.; Rosario, F.; Chan, J.; Cox, L. A.; Ferchaud-Roucher, V.; Zemski-Berry, K.; Reusch, J.; Keller, A.; Powell, T.; Jansson, T.

doi:10.1101/2021.09.15.460457

bioRxiv · 10.1101/2021.09.15.460457

Maternal obesity causes fetal cardiac hypertrophy and alters adult offspring myocardial metabolism in mice

Vaughan, O. R.·Rosario, F.·Chan, J.·Cox, L. A.·Ferchaud-Roucher, V.·Zemski-Berry, K.·Reusch, J.·Keller, A.·Powell, T.·Jansson, T.

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Abstract

Obesity in pregnant women causes fetal cardiac dysfunction and increases offspring cardiovascular disease risk but its effect on myocardial metabolism is unknown. We hypothesised that maternal obesity alters fetal cardiac expression of metabolism-related genes and shifts offspring myocardial substrate preference from glucose towards lipids. Female mice were fed control or obesogenic diets before and during pregnancy. Fetal hearts were studied in late gestation (embryonic day, E18.5; term{approx}E21) and offspring were studied at 3, 6, 9 or 24 months postnatally. Maternal obesity increased heart weight and peroxisome proliferator activated receptor {gamma} (Pparg) expression in female and male fetuses and caused left ventricular diastolic dysfunction in the adult offspring. Cardiac dysfunction progressively worsened with age in female, not male, offspring of obese dams, compared to age-matched controls. In 6-month-old offspring, exposure to maternal obesity increased cardiac palmitoyl carnitine-supported mitochondrial respiration in males and reduced myocardial 18F-fluorodeoxyglucose uptake in females. Cardiac Pparg expression remained higher in adult offspring of obese than control dams and correlated with contractile and metabolic function. Maternal obesity did not affect cardiac palmitoyl carnitine respiration in females or 18F-fluorodeoxyglucose uptake in males, or alter cardiac 3H-oleic acid uptake, pyruvate respiration, lipid content or fatty acid/glucose transporter abundance in offspring of either sex. The results support our hypothesis and show that maternal obesity affects offspring cardiac metabolism in a sex-dependent manner. Persistent upregulation of Pparg expression in response to overnutrition in utero may mechanistically underpin programmed cardiac impairments and contribute to cardiovascular disease risk in children of women with obesity.

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Vaughan, O. R., Rosario, F., Chan, J., Cox, L. A., Ferchaud-Roucher, V., Zemski-Berry, K., Reusch, J., Keller, A., Powell, T., Jansson, T.. 2021-09-16. Maternal obesity causes fetal cardiac hypertrophy and alters adult offspring myocardial metabolism in mice. https://doi.org/10.1101/2021.09.15.460457

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