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| Item Type: | Article |
|---|---|
| Title: | Diabetic pregnancy as a novel risk factor for cardiac dysfunction in the offspring-the heart as a target for fetal programming in rats |
| Creators Name: | Schütte, T. and Kedziora, S.M. and Haase, N. and Herse, F. and Alenina, N. and Müller, D.N. and Bader, M. and Schupp, M. and Dechend, R. and Golic, M. and Kräker, K. |
| Abstract: | AIMS/HYPOTHESIS: The impact of diabetic pregnancy has been investigated extensively regarding offspring metabolism; however, little is known about the influence on the heart. We aimed to characterise the effects of a diabetic pregnancy on male adult offspring cardiac health after feeding a high-fat diet in an established transgenic rat model. METHODS: We applied our rat model for maternal type 2 diabetes characterised by maternal insulin resistance with hyperglycaemia and hyperinsulinaemia. Diabetes was induced preconceptionally via doxycycline-induced knock down of the insulin receptor in transgenic rats. Male wild-type offspring of diabetic and normoglycaemic pregnancies were raised by foster mothers, followed up into adulthood and subgroups were challenged by a high-fat diet. Cardiac phenotype was assessed by innovative speckle tracking echocardiography, circulating factors, immunohistochemistry and gene expression in the heart. RESULTS: When feeding normal chow, we did not observe differences in cardiac function, gene expression and plasma brain natriuretic peptide between adult diabetic or normoglycaemic offspring. Interestingly, when being fed a high-fat diet, adult offspring of diabetic pregnancy demonstrated decreased global longitudinal (-14.82 ± 0.59 vs -16.60 ± 0.48%) and circumferential strain (-23.40 ± 0.57 vs -26.74 ± 0.34%), increased relative wall thickness (0.53 ± 0.06 vs 0.37 ± 0.02), altered cardiac gene expression, enlarged cardiomyocytes (106.60 ± 4.14 vs 87.94 ± 1.67 μm), an accumulation of immune cells in the heart (10.27 ± 0.30 vs 6.48 ± 0.48 per fov) and higher plasma brain natriuretic peptide levels (0.50 ± 0.12 vs 0.12 ± 0.03 ng/ml) compared with normoglycaemic offspring on a high-fat diet. Blood pressure, urinary albumin, blood glucose and body weight were unaltered between groups on a high-fat diet. CONCLUSIONS/INTERPRETATION: Diabetic pregnancy in rats induces cardiac dysfunction, left ventricular hypertrophy and altered proinflammatory status in adult offspring only after a high-fat diet. A diabetic pregnancy itself was not sufficient to impair myocardial function and gene expression in male offspring later in life. This suggests that a postnatal high-fat diet is important for the development of cardiac dysfunction in rat offspring after diabetic pregnancy. Our data provide evidence that a diabetic pregnancy is a novel cardiac risk factor that becomes relevant when other challenges, such as a high-fat diet, are present. |
| Keywords: | Cardiovascular Diseases, Diabetes Mellitus, Diet, Echocardiography, High-Fat, Hyperglycaemia, Infant, Maternal Inheritance, Pregnancy, Transgenic, Animals, Rats |
| Source: | Diabetologia |
| ISSN: | 0012-186X |
| Publisher: | Springer |
| Volume: | 64 |
| Number: | 12 |
| Page Range: | 2829-2842 |
| Date: | December 2021 |
| Official Publication: | https://doi.org/10.1007/s00125-021-05566-5 |
| PubMed: | View item in PubMed |
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