Abstract 986: Maternal Fat Intake Alters Gene Expression And Heart Size In Adult Offspring
Background: Obesity is epidemic in the United States and much of the world. Whereas the effects of high fat intake on the health of the individual has been the focus of significant examination, the effects of maternal dietary factors, such as a high fat intake during preganancy, on the cardiovascular phenotype of the offspring has remained unclear.
Methods: Pregnant female BL6C57 mice were fed either a high fat diet or normal chow. The offspring of these pregnancies were sacrificed either during mid-gestation, immediately post-birth, or as adults, and were examined by in situ hybridization, Real-time RT-PCR, Western blot, and histological and morphological methods to determine the effects of the maternal high fat intake on the cardiovascular system.
Results: In the placentas of high fat diet pregnancies there was a significant increase in the expression of HIF-1alpha and HIF-regulated genes, suggesting either placental hypoxia, or a non-oxygen related alteration in the placenta secondary to the high fat diet. Concomitantly, developmental vascular morphogenesis was significantly altered in the offspring of high fat pregnancies, demonstrating decreased vascularization and diminished branching. The heart weights of the adult (9 weeks age) offspring of these pregnancies were significantly increased, averaging 10 –15% higher than syngeneic offspring of mothers fed normal chow. This was accompanied by significant differences in the myocardial expression of specific genes, including VEGF, HIF, Glut1 and Glut4.
Conclusions: These data suggest that maternal fat intake has substantive effects cardiovascular morphology and gene expression in the adult offspring of these pregnancies. Whether such alterations are purely developmental in nature, reflect an epigenetic mechanism, or a combination of these remains unclear, but the implications to human health are substantial.