Reduced in utero substrate supply decreases mitochondrial abundance and alters the expression of metabolic signalling molecules in the fetal sheep heart

被引：4

作者：

Dimasi, Catherine G. ^{[1
]}

Darby, Jack R. T. ^{[1
]}

Cho, Steven K. S. ^{[1
,2
]}

Saini, Brahmdeep S. ^{[1
,3
]}

Holman, Stacey L. ^{[1
]}

Meakin, Ashley S. ^{[1
]}

Wiese, Michael D. ^{[1
]}

Macgowan, Christopher K. ^{[3
,4
]}

Seed, Mike ^{[2
,3
,5
]}

Morrison, Janna L. ^{[1
,2
,3
]}

机构：

[1] Univ South Australia, Early Origins Adult Hlth Res Grp, Hlth & Biomed Innovat, UniSA Clin & Hlth Sci, GPO Box 2471, Adelaide, SA 5001, Australia

[2] Univ Toronto, Temerty Fac Med, Dept Physiol, Toronto, ON, Canada

[3] Hosp Sick Children, Res Inst, Peter Gilgan Ctr Res & Learning, Toronto, ON, Canada

[4] Univ Toronto, Temerty Fac Med, Dept Med Biophys, Toronto, ON, Canada

[5] Univ Toronto, Hosp Sick Children, Dept Pediat, Div Cardiol, Toronto, ON, Canada

来源：

JOURNAL OF PHYSIOLOGY-LONDON | 2023年

基金：

加拿大健康研究院;

关键词：

cardiac output; fetus; FGR; hypoxia; IUGR; magnetic resonance imaging; metabolism; mitochondria; INTRAUTERINE GROWTH RESTRICTION; LOW-BIRTH-WEIGHT; MATERNAL FLUOXETINE INFUSION; GESTATIONAL-AGE INFANTS; CELL-CYCLE ACTIVITY; CARDIAC METABOLISM; THYROID-HORMONE; PLACENTAL INSUFFICIENCY; GLUCOSE-METABOLISM; PREGNANT SHEEP;

D O I：

10.1113/JP285572

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Babies born with fetal growth restriction (FGR) are at higher risk of developing cardiometabolic diseases across the life course. The reduction in substrate supply to the developing fetus that causes FGR not only alters cardiac growth and structure but may have deleterious effects on metabolism and function. Using a sheep model of placental restriction to induce FGR, we investigated key cardiac metabolic and functional markers that may be altered in FGR. We also employed phase-contrast magnetic resonance imaging MRI to assess left ventricular cardiac output (LVCO) as a measure of cardiac function. We hypothesized that signalling molecules involved in cardiac fatty acid utilisation and contractility would be impaired by FGR and that this would have a negative impact on LVCO in the late gestation fetus. Key glucose (GLUT4 protein) and fatty acid (FATP, CD36 gene expression) substrate transporters were significantly reduced in the hearts of FGR fetuses. We also found reduced mitochondrial numbers as well as abundance of electron transport chain complexes (complexes II and IV). These data suggest that FGR diminishes metabolic and mitochondrial capacity in the fetal heart; however, alterations were not correlated with fetal LVCO. Overall, these data show that FGR alters fetal cardiac metabolism in late gestation. If sustained ex utero, this altered metabolic profile may contribute to poor cardiac outcomes in FGR-born individuals after birth.

引用

页数：22