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Placental insufficiency induces a sexually dimorphic response in the expression of cardiac growth and metabolic signalling molecules upon exposure to a postnatal western diet in guinea pigs

Published online by Cambridge University Press:  26 July 2021

Jack R.T. Darby
Affiliation:
Early Origins of Adult Health Research Group, Health and Biomedical Innovation, UniSA: Clinical and Health Sciences, University of South Australia, Adelaide, SA, Australia
Jacky Chiu
Affiliation:
Physiology and Pharmacology, Western University, London, ON, Canada
Timothy R.H. Regnault
Affiliation:
Departments of Obstetrics and Gynaecology, Western University, London, ON, Canada Physiology and Pharmacology, Western University, London, ON, Canada Children’s Health Research Institute and Lawson Health Research Institute, London, ON, Canada
Janna L. Morrison*
Affiliation:
Early Origins of Adult Health Research Group, Health and Biomedical Innovation, UniSA: Clinical and Health Sciences, University of South Australia, Adelaide, SA, Australia
*
Address for correspondence: Janna L. Morrison, PhD., ARC Future Fellow (Level 3), Early Origins of Adult Health Research Group, Health and Biomedical Innovation, UniSA Clinical and Health Sciences, University of South Australia, GPO Box 2471, Adelaide, SA, Australia. Email: [email protected]

Abstract

There is a strong relationship between low birth weight (LBW) and an increased risk of developing cardiovascular disease (CVD). In postnatal life, LBW offspring are becoming more commonly exposed to the additional independent CVD risk factors, such as an obesogenic diet. However, how an already detrimentally programmed LBW myocardium responds to a secondary insult, such as an obesogenic diet (western diet; WD), during postnatal life is ill defined. Herein, we aimed to determine in a pre-clinical guinea pig model of CVD, both the independent and interactive effects of LBW and a postnatal WD on the molecular pathways that regulate cardiac growth and metabolism. Uterine artery ablation was used to induce placental insufficiency (PI) in pregnant guinea pigs to generate LBW offspring. Normal birth weight (NBW) and LBW offspring were weaned onto either a Control diet or WD. At ˜145 days after birth (young adulthood), male and female offspring were humanely killed, the heart weighed and left ventricle tissue collected. The mRNA expression of signalling molecules involved in a pathological hypertrophic and fibrotic response was increased in the myocardium of LBW male, but not female offspring, fed a WD as was the mRNA expression of transcription factors involved in fatty acid oxidation. The mRNA expression of glucose transporters was downregulated by LBW and WD in male, but not female hearts. This study has highlighted a sexually dimorphic cardiac pathological hypertrophic and fibrotic response to the secondary insult of postnatal WD consumption in LBW offspring.

Type
Original Article
Copyright
© The Author(s), 2021. Published by Cambridge University Press in association with International Society for Developmental Origins of Health and Disease

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Footnotes

*

Denotes equal contribution.

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