Maternal diabetes causes coordinated down-regulation of genes involved with lipid metabolism in the murine fetal heart

Maternal diabetes is associated with increased transport of lipids to the fetus and increased risk of hypertrophic cardiomyopathy in the fetus. During fetal life, the heart normally has limited capacity to use lipids as fuel; and, at least in adults, cardiac lipid accumulation may lead to cardiomyopathy. Postnatally, lipid supply is increased when the offspring begins to suckle. We examined offspring from hypoinsulinemic Ins2Akita mice to assess whether maternal diabetes results in fetal myocardial hypertrophy and triglyceride accumulation and compared these with fetal hearts collected postnatally. On embryonic days 16 to 19, the fetal heart weight and triglyceride content were similar in offspring from Ins2Akita and nondiabetic wild-type mothers. The heart expression of lipid-metabolizing genes (peroxisomal proliferator-activated receptor α, lipoprotein lipase, fatty acid translocase, and fatty acid transport protein 1) was reduced in offspring from Ins2Akita mothers with high blood glucose levels and were closely intercorrelated, suggesting coordinated down-regulation. In contrast, on day 1 postnatally where the lipid availability to the heart is markedly increased, heart triglycerides and expression of several lipid-metabolizing genes (including lipoprotein lipase and fatty acid transport protein 1) were increased in offspring from wild-type mice. The results suggest that maternal type 1 diabetes mellitus in Ins2Akita mice does not cause cardiac hypertrophy or triglycerides accumulation in the fetal heart, possibly because of a coordinated down-regulation of genes controlling fatty acid uptake.