Age and Sex Influence Mitochondria and Cardiac Health in Offspring Exposed to Maternal Glucolipotoxicity
| Autor: | Julie A. Eclov, Ruthellen H. Anderson, Tricia D. Larsen, Tyler C T Gandy, Kennedy S. Mdaki, Michelle L. Baack, Katherine A. Kern, Todd C Rideout, Angela L. Wachal, Jacob T. Cain, Eli J. Louwagie |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cardiac function curve medicine.medical_specialty Bioenergetics Heart disease Offspring Physiology Cardiomyopathy 02 engineering and technology Mitochondrion Article 03 medical and health sciences Internal medicine Mitophagy Medicine Animal Physiology Myocardial infarction Molecular Biology Multidisciplinary business.industry Diabetology Cell Biology Biological Sciences 021001 nanoscience & nanotechnology medicine.disease 030104 developmental biology Endocrinology 0210 nano-technology business |
| Zdroj: | iScience |
| ISSN: | 2589-0042 |
| Popis: | Summary Infants of diabetic mothers are at risk of cardiomyopathy at birth and myocardial infarction in adulthood, but prevention is hindered because mechanisms remain unknown. We previously showed that maternal glucolipotoxicity increases the risk of cardiomyopathy and mortality in newborn rats through fuel-mediated mitochondrial dysfunction. Here we demonstrate ongoing cardiometabolic consequences by cross-fostering and following echocardiography, cardiomyocyte bioenergetics, mitochondria-mediated turnover, and cell death following metabolic stress in aged adults. Like humans, cardiac function improves by weaning with no apparent differences in early adulthood but declines again in aged diabetes-exposed offspring. This is preceded by impaired oxidative phosphorylation, exaggerated age-related increase in mitochondrial number, and higher oxygen consumption. Prenatally exposed male cardiomyocytes have more mitolysosomes indicating high baseline turnover; when exposed to metabolic stress, mitophagy cannot increase and cardiomyocytes have faster mitochondrial membrane potential loss and mitochondria-mediated cell death. Details highlight age- and sex-specific roles of mitochondria in developmentally programmed adult heart disease. Graphical Abstract Highlights • Fetal exposures disrupt mitochondria, bioenergetics, & cardiac function at birth • First, bioenergetics & function improve until greater reliance on OXPHOS with age • At 6MO, poor respiration incites biogenesis & mitophagy, and then functional decline • Fetal exposures cause faster mitochondria-mediated cell death in aged adult hearts Biological Sciences; Physiology; Animal Physiology; Molecular Biology; Diabetology; Cell Biology |
| Databáze: | OpenAIRE |
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