Mitochondrial Transfer Improves Cardiomyocyte Bioenergetics and Viability in Male Rats Exposed to Pregestational Diabetes
Offspring born to diabetic or obese mothers have a higher lifetime risk of heart disease. Previously, we found that rat offspring exposed to late-gestational diabetes mellitus (LGDM) and maternal high-fat (HF) diet develop mitochondrial dysfunction, impaired cardiomyocyte bioenergetics, and cardiac...
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MDPI AG
2021-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/5/2382 |
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| author | Eli J. Louwagie Tricia D. Larsen Angela L. Wachal Tyler C.T. Gandy Michelle L. Baack |
| author_facet | Eli J. Louwagie Tricia D. Larsen Angela L. Wachal Tyler C.T. Gandy Michelle L. Baack |
| author_sort | Eli J. Louwagie |
| collection | DOAJ |
| description | Offspring born to diabetic or obese mothers have a higher lifetime risk of heart disease. Previously, we found that rat offspring exposed to late-gestational diabetes mellitus (LGDM) and maternal high-fat (HF) diet develop mitochondrial dysfunction, impaired cardiomyocyte bioenergetics, and cardiac dysfunction at birth and again during aging. Here, we compared echocardiography, cardiomyocyte bioenergetics, oxidative damage, and mitochondria-mediated cell death among control, pregestational diabetes mellitus (PGDM)-exposed, HF-diet-exposed, and combination-exposed newborn offspring. We hypothesized that PGDM exposure, similar to LGDM, causes mitochondrial dysfunction to play a central, pathogenic role in neonatal cardiomyopathy. We found that PGDM-exposed offspring, similar to LGDM-exposed offspring, have cardiac dysfunction at birth, but their isolated cardiomyocytes have seemingly less bioenergetics impairment. This finding was due to confounding by impaired viability related to poorer ATP generation, more lipid peroxidation, and faster apoptosis under metabolic stress. To mechanistically isolate and test the role of mitochondria, we transferred mitochondria from normal rat myocardium to control and exposed neonatal rat cardiomyocytes. As expected, transfer provides a respiratory boost to cardiomyocytes from all groups. They also reduce apoptosis in PGDM-exposed males, but not in females. Findings highlight sex-specific differences in mitochondria-mediated mechanisms of developmentally programmed heart disease and underscore potential caveats of therapeutic mitochondrial transfer. |
| first_indexed | 2024-03-09T06:17:54Z |
| format | Article |
| id | doaj.art-917c533280434c55a65fbdceb591e568 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T06:17:54Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-917c533280434c55a65fbdceb591e5682023-12-03T11:51:03ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-02-01225238210.3390/ijms22052382Mitochondrial Transfer Improves Cardiomyocyte Bioenergetics and Viability in Male Rats Exposed to Pregestational DiabetesEli J. Louwagie0Tricia D. Larsen1Angela L. Wachal2Tyler C.T. Gandy3Michelle L. Baack4Sanford School of Medicine, University of South Dakota, Sioux Falls, SD 57105, USAEnvironmental Influences on Health and Disease Group, Sanford Research, Sioux Falls, SD 57104, USAEnvironmental Influences on Health and Disease Group, Sanford Research, Sioux Falls, SD 57104, USAEnvironmental Influences on Health and Disease Group, Sanford Research, Sioux Falls, SD 57104, USASanford School of Medicine, University of South Dakota, Sioux Falls, SD 57105, USAOffspring born to diabetic or obese mothers have a higher lifetime risk of heart disease. Previously, we found that rat offspring exposed to late-gestational diabetes mellitus (LGDM) and maternal high-fat (HF) diet develop mitochondrial dysfunction, impaired cardiomyocyte bioenergetics, and cardiac dysfunction at birth and again during aging. Here, we compared echocardiography, cardiomyocyte bioenergetics, oxidative damage, and mitochondria-mediated cell death among control, pregestational diabetes mellitus (PGDM)-exposed, HF-diet-exposed, and combination-exposed newborn offspring. We hypothesized that PGDM exposure, similar to LGDM, causes mitochondrial dysfunction to play a central, pathogenic role in neonatal cardiomyopathy. We found that PGDM-exposed offspring, similar to LGDM-exposed offspring, have cardiac dysfunction at birth, but their isolated cardiomyocytes have seemingly less bioenergetics impairment. This finding was due to confounding by impaired viability related to poorer ATP generation, more lipid peroxidation, and faster apoptosis under metabolic stress. To mechanistically isolate and test the role of mitochondria, we transferred mitochondria from normal rat myocardium to control and exposed neonatal rat cardiomyocytes. As expected, transfer provides a respiratory boost to cardiomyocytes from all groups. They also reduce apoptosis in PGDM-exposed males, but not in females. Findings highlight sex-specific differences in mitochondria-mediated mechanisms of developmentally programmed heart disease and underscore potential caveats of therapeutic mitochondrial transfer.https://www.mdpi.com/1422-0067/22/5/2382mitochondriadiabetic pregnancydevelopmentally programmed heart diseasemitochondrial transfer |
| spellingShingle | Eli J. Louwagie Tricia D. Larsen Angela L. Wachal Tyler C.T. Gandy Michelle L. Baack Mitochondrial Transfer Improves Cardiomyocyte Bioenergetics and Viability in Male Rats Exposed to Pregestational Diabetes International Journal of Molecular Sciences mitochondria diabetic pregnancy developmentally programmed heart disease mitochondrial transfer |
| title | Mitochondrial Transfer Improves Cardiomyocyte Bioenergetics and Viability in Male Rats Exposed to Pregestational Diabetes |
| title_full | Mitochondrial Transfer Improves Cardiomyocyte Bioenergetics and Viability in Male Rats Exposed to Pregestational Diabetes |
| title_fullStr | Mitochondrial Transfer Improves Cardiomyocyte Bioenergetics and Viability in Male Rats Exposed to Pregestational Diabetes |
| title_full_unstemmed | Mitochondrial Transfer Improves Cardiomyocyte Bioenergetics and Viability in Male Rats Exposed to Pregestational Diabetes |
| title_short | Mitochondrial Transfer Improves Cardiomyocyte Bioenergetics and Viability in Male Rats Exposed to Pregestational Diabetes |
| title_sort | mitochondrial transfer improves cardiomyocyte bioenergetics and viability in male rats exposed to pregestational diabetes |
| topic | mitochondria diabetic pregnancy developmentally programmed heart disease mitochondrial transfer |
| url | https://www.mdpi.com/1422-0067/22/5/2382 |
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