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Maternal High‐fat Diet and Diabetes Impairs Cardiac Metabolism and Mitochondrial Dynamics in Adult Offspring of Diabetic Pregnancy
Author(s) -
Mdaki Kennedy S,
Larsen Tricia D,
Louwagie Eli J,
Baack Michelle L
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.lb608
Subject(s) - offspring , medicine , endocrinology , diabetes mellitus , pregnancy , gestational diabetes , oxidative stress , gestation , streptozotocin , biology , genetics
Background Offspring of diabetic mothers are at risk of cardiovascular disease at birth and throughout life. We recently reported that maternal high‐fat (HF) diet impairs cardiac function in newborn offspring of diabetic pregnancy through metabolic stress and mitochondrial dysfunction. Whether this in utero exposure to maternal hyperglycemia and dyslipidemia can have lasting consequences on the developing heart is still unknown. Objective To determine the long‐term effects of prenatal exposure to maternal diabetes and high‐fat (HF) diet on cardiac metabolism in the adult offspring. Methods Female Sprague Dawley rats received controlled (CD) or HF diet throughout the study. At gestational day 14, dams were injected with either citrate buffer (CB) placebo or streptozotocin (STZ) to induce diabetes producing offspring from the following groups: controls (CD‐CB), diabetic exposed (CD‐STZ), HF exposed (HF‐CB), and combination exposed (HF‐STZ). Litters were culled to equal size and pups were cross‐fostered to normal dams. Cellular bioenergetics, oxidative injury, and mitochondrial dynamics were evaluated using Seahorse® XF24 analyses, malondialdehyde assay, and confocal live cell imaging of primary isolated cardiomyocytes from offspring at 6 months of age. Outcomes were interrogated for diet, diabetes and interaction effect using ANOVA with significance set at p≤0.05. Results HF diet‐exposed cardiomyocytes demonstrated abnormal cardiac bioenergetics profiles, increased lipid peroxidation, and a relatively decreased ability to recover from FCCP challenge with signs of mitochondrial dysfunction on live cell imaging. Combination‐exposed cardiomyocytes were most severely affected. Conclusion Late gestation diabetes alters cardiac metabolism in the developing heart and the effects are exacerbated with prenatal exposure to a maternal HF diet. These cardiometabolic consequences persist into adulthood. The FCCP challenge demonstrates that combination exposed offspring have an impaired ability to maintain ATP production under stress which is a significant risk factor for heart disease. Together, our findings highlight that cardiac metabolism plays a significant role in developmentally programmed cardiovascular disease in offspring of diabetic pregnancy. Support or Funding Information NIH‐NICHD K08HD078504, Sanford Research, SSOM‐USD Faculty Grant, Sanford Health– SDSU Collaborative Research Seed Grant, Institutional Development Awards (IDeA) NIH ‐GMS P20GM103620‐01A1 (Pediatrics) and P20GM103548 (Cancer) COBRE grants