{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T07:57:57Z","timestamp":1787731077726,"version":"build-2784847793"},"reference-count":81,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2019,6,25]],"date-time":"2019-06-25T00:00:00Z","timestamp":1561420800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K08HD078504"],"award-info":[{"award-number":["K08HD078504"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P20GM103620"],"award-info":[{"award-number":["P20GM103620"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["DBI-1262744"],"award-info":[{"award-number":["DBI-1262744"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["IIA-1355423"],"award-info":[{"award-number":["IIA-1355423"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/ijms20123090","type":"journal-article","created":{"date-parts":[[2019,6,25]],"date-time":"2019-06-25T10:52:31Z","timestamp":1561459951000},"page":"3090","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["Diabetic Pregnancy and Maternal High-Fat Diet Impair Mitochondrial Dynamism in the Developing Fetal Rat Heart by Sex-Specific Mechanisms"],"prefix":"10.3390","volume":"20","author":[{"given":"Tricia D.","family":"Larsen","sequence":"first","affiliation":[{"name":"Environmental Influences on Health and Disease Group, Sanford Research, 2301 E 60th Street North, Sioux Falls, SD 57104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyle H.","family":"Sabey","sequence":"additional","affiliation":[{"name":"Sanford School of Medicine of the University of South Dakota, Sioux Falls, SD 57117, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexis J.","family":"Knutson","sequence":"additional","affiliation":[{"name":"Environmental Influences on Health and Disease Group, Sanford Research, 2301 E 60th Street North, Sioux Falls, SD 57104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tyler C. T.","family":"Gandy","sequence":"additional","affiliation":[{"name":"Environmental Influences on Health and Disease Group, Sanford Research, 2301 E 60th Street North, Sioux Falls, SD 57104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eli J.","family":"Louwagie","sequence":"additional","affiliation":[{"name":"Environmental Influences on Health and Disease Group, Sanford Research, 2301 E 60th Street North, Sioux Falls, SD 57104, USA"},{"name":"Sanford School of Medicine of the University of South Dakota, Sioux Falls, SD 57117, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lothar","family":"Lauterboeck","sequence":"additional","affiliation":[{"name":"Environmental Influences on Health and Disease Group, Sanford Research, 2301 E 60th Street North, Sioux Falls, SD 57104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kennedy S.","family":"Mdaki","sequence":"additional","affiliation":[{"name":"Environmental Influences on Health and Disease Group, Sanford Research, 2301 E 60th Street North, Sioux Falls, SD 57104, USA"},{"name":"Barshop Institute for Longevity and Aging Studies, UT Health, San Antonio, TX 78245, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle L.","family":"Baack","sequence":"additional","affiliation":[{"name":"Environmental Influences on Health and Disease Group, Sanford Research, 2301 E 60th Street North, Sioux Falls, SD 57104, USA"},{"name":"Sanford School of Medicine of the University of South Dakota, Sioux Falls, SD 57117, USA"},{"name":"Boekelheide Neonatal Intensive Care Unit, Sanford Children\u2019s Hospital, Sioux Falls, SD 57117, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,6,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1007\/s00246-003-0538-8","article-title":"Congenital heart disease in infants of diabetic mothers: Echocardiographic study","volume":"25","author":"Subaih","year":"2004","journal-title":"Pediatr. 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