title: Maternal diabetes causes coordinated down-regulation of genes involved with lipid metabolism in the murine fetal heart.
abstract: 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 Ins2(Akita) 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 Ins2(Akita) and nondiabetic wild-type mothers. The heart expression of lipid-metabolizing genes (peroxisomal proliferator-activated receptor alpha, lipoprotein lipase, fatty acid translocase, and fatty acid transport protein 1) was reduced in offspring from Ins2(Akita) 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 Ins2(Akita) 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.
authors.affiliation: Department of Clinical Biochemistry, Rigshospitalet, 2100 Copenhagen, Denmark. marie_lasse@dadlnet.dk
authors.forename: Marie L S
authors.initials: ML
authors.lastname: Lindegaard
authors.forename: Lars B
authors.initials: LB
authors.lastname: Nielsen
mesh_terms: D000818:Animals; D016640:Diabetes, Gestational / Q000378:metabolism*; D015536:Down-Regulation; D050612:Fatty Acid Transport Proteins / Q000235:genetics; D005260:Female; D005318:Fetal Heart / Q000378:metabolism*; D005786:Gene Expression Regulation; D008071:Lipoprotein Lipase / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020097:Natriuretic Peptide, Brain / Q000235:genetics; D047493:PPAR alpha / Q000235:genetics; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011247:Pregnancy; D015534:Trans-Activators / Q000235:genetics; D014157:Transcription Factors; D014280:Triglycerides / Q000378:metabolism*
chemical_list: D050612:Fatty Acid Transport Proteins; D047493:PPAR alpha; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; C493569:Slc27a1 protein, mouse; C493572:Slc27a4 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D014280:Triglycerides; D020097:Natriuretic Peptide, Brain; D008071:Lipoprotein Lipase