A mechanistic examination of the impact of maternal high-fat diet on long-term offspring obesity risk.

Abstract

Obesity is currently at epidemic rates in the United States, and this includes a large percentage of women of child-bearing age. It is clear that maternal obesity significantly increases the rates of birth defects, maternal complications, fetal loss, and the incidence of large for gestational age (LGA) infants. Equally intriguing is the emerging relationship between maternal obesity and the predisposition of children born of these pregnancies having an increased risk for overweight and obesity as adults. Elucidation of the possible mechanisms by which the intrauterine environment transmits these signals and impacts fetal development is necessary. To investigate these parameters, we have examined changes in expression levels for hypothalamic POMC and NPY in 3-week-old offspring from dams on a high-fat diet during pregnancy. Compared to controls, these mice show significant changes in POMC levels. No differences were found in NPY expression. As the offspring from high-fat diet dams weighed significantly more at this age, alterations in POMC expression may support epigenetic regulation resulting from a high nutritional state during development. We have begun examination of changes in DNA methylation of specific genes related to maternal dietary status. Results from our proposed work will provide significant insight into the underlying causes of the potential long-term risk for development of overweight or obesity associated with an obese intrauterine environment.