Format

Send to

Choose Destination
Int J Mol Sci. 2019 Jun 25;20(12). pii: E3090. doi: 10.3390/ijms20123090.

Diabetic Pregnancy and Maternal High-Fat Diet Impair Mitochondrial Dynamism in the Developing Fetal Rat Heart by Sex-Specific Mechanisms.

Author information

1
Environmental Influences on Health and Disease Group, Sanford Research, 2301 E 60th Street North, Sioux Falls, SD 57104, USA. tricia.larsen@sanfordhealth.org.
2
Sanford School of Medicine of the University of South Dakota, Sioux Falls, SD 57117, USA. kyle.sabey@sanfordhealth.org.
3
Environmental Influences on Health and Disease Group, Sanford Research, 2301 E 60th Street North, Sioux Falls, SD 57104, USA. ajknutson15@ole.augie.edu.
4
Environmental Influences on Health and Disease Group, Sanford Research, 2301 E 60th Street North, Sioux Falls, SD 57104, USA. tyler.gandy@sanfordhealth.org.
5
Environmental Influences on Health and Disease Group, Sanford Research, 2301 E 60th Street North, Sioux Falls, SD 57104, USA. eli.louwagie@sanfordhealth.org.
6
Sanford School of Medicine of the University of South Dakota, Sioux Falls, SD 57117, USA. eli.louwagie@sanfordhealth.org.
7
Environmental Influences on Health and Disease Group, Sanford Research, 2301 E 60th Street North, Sioux Falls, SD 57104, USA. llaute@lsuhsc.edu.
8
Environmental Influences on Health and Disease Group, Sanford Research, 2301 E 60th Street North, Sioux Falls, SD 57104, USA. mdaki@uthscsa.edu.
9
Barshop Institute for Longevity and Aging Studies, UT Health, San Antonio, TX 78245, USA. mdaki@uthscsa.edu.
10
Environmental Influences on Health and Disease Group, Sanford Research, 2301 E 60th Street North, Sioux Falls, SD 57104, USA. michelle.baack@sanfordhealth.org.
11
Sanford School of Medicine of the University of South Dakota, Sioux Falls, SD 57117, USA. michelle.baack@sanfordhealth.org.
12
Boekelheide Neonatal Intensive Care Unit, Sanford Children's Hospital, Sioux Falls, SD 57117, USA. michelle.baack@sanfordhealth.org.

Abstract

Infants born to diabetic or obese mothers are at greater risk of heart disease at birth and throughout life, but prevention is hindered because underlying mechanisms remain poorly understood. Using a rat model, we showed that prenatal exposure to maternal diabetes and a high-fat diet caused diastolic and systolic dysfunction, myocardial lipid accumulation, decreased respiratory capacity, and oxidative stress in newborn offspring hearts. This study aimed to determine whether mitochondrial dynamism played a role. Using confocal live-cell imaging, we examined mitochondrial dynamics in neonatal rat cardiomyocytes (NRCM) from four prenatally exposed groups: controls, diabetes, high-fat diet, and combination exposed. Cardiac expression of dynamism-related genes and proteins were compared, and gender-specific differences were evaluated. Findings show that normal NRCM have highly dynamic mitochondria with a well-balanced number of fusion and fission events. Prenatal exposure to diabetes or a high-fat diet impaired dynamism resulting in shorter, wider mitochondria. Mechanisms of impaired dynamism were gender-specific and protein regulated. Females had higher expression of fusion proteins which may confer a cardioprotective effect. Prenatally exposed male hearts had post-translational modifications known to impair dynamism and influence mitophagy-mediated cell death. This study identifies mitochondrial fusion and fission proteins as targetable, pathogenic regulators of heart health in offspring exposed to excess circulating maternal fuels.

KEYWORDS:

cardiovascular disease; maternal diabetes; maternal high-fat diet; mitochondrial dynamism; sex-specific mechanisms of the developmental origins of health and disease (DOHaD)

Supplemental Content

Full text links

Icon for Multidisciplinary Digital Publishing Institute (MDPI) Icon for PubMed Central
Loading ...
Support Center