Maternal Diet and Epigenetic Programming in utero

The Fetal Origin of Adult disease hypothesis suggests adverse environmental factors acting in utero program the development of fetal tissues, producing later dysfunctions and diseases. Epigenetic events established early in life, such as patterns of DNA methylation or histone acetylation, and in response to environmental conditions, may provide a mechanism that can account for predisposing individuals to later-in-life diseases. We have been testing the hypothesis that in utero exposure to a maternal L ow P rotein D iet (LPD) or H i F at D iet (HFD) during preimplantation development, then through gestation, or through gestation plus lactation programs expression of epigenetically regulated genes in organs of mice and that the expression patterns persist into later life.

Fat Avoidance in Acads -Deficient Mice

This study investigates the interactions among genes and dietary macronutrients in a genetic model of impaired fatty acid oxidation. A mouse inbred strain with a single gene mutation in Acads (short chain acyl-CoA dehydrogenase) avoids eating fat in choice diet paradigms, a behavior that could be initiated by changes in fat metabolism. Using DNA microarrays, patterns of gene expression in selected brain regions will be compared between mutant and non-mutant mice ingesting high- or low-fat diets. Thus the subset of genes activated by the metabolic response to fat intake in Acads -deficient mice will be identified. The discovery of candidate genes/pathways underlying fat avoidance in this new model will increase our understanding of the metabolic regulation of food intake.

Genetics and Binge Eating: A Case-Control Pilot Study

Genes, behaviors, and the environment are intimately related in the etiology and maintenance of obesity. Further, the effects of the genotype can be amplified in an environment that promotes obesity. This pilot study aims to identify genetic markers that are associated with the presence of binge eating behavior (behavioral phenotype). The primary aim of the study is to investigate the association of a behavioral phenotype, binge eating, with the melanocortin system. The primary hypothesis is that the presence of mutation in the MC4 receptor is associated with a binge eating phenotype, which may contribute to the development of obesity. The proposed pilot study will produce novel data on the relationship between genes and binge eating. This study is designed to be the first in a series of studies to investigate the relationship between genotypes and extreme eating behaviors in humans. This research may mark the beginnings of the attainment of knowledge towards the development of treatment programs and/or medications to be utilized in the future treatment of binge eating and/or obesity.