Poster 26
Presenter: Brian Parks
Thursday, 4:00 – 6:00pm
Brian W. Parks1, Elizabeth Nam1, Emrah Kostem3, Eleazar Eskin3, Aldons J. Lusis1,2 1Departments of Medicine/Division of Cardiology, 2Human Genetics, and 3Computer Science, University of California, Los Angeles
Consumption of a high-fat diet rich in refined carbohydrates is a key environmental factor driving the worldwide obesity epidemic. To understand the genetic and biological pathways contributing to obesity we employed a powerful systems genetics approach in the mouse capable of high-resolution genome-wide association mapping and integration of traits across multiple scales of biology (DNA, RNA, Protein, and Metabolite). We fed more than 100 unique inbred strains of male and female mice a high-fat/high-sucrose (HF/HS) diet. Mice were fed HF/HS diet for 8 weeks and body composition was measured every two weeks using magnetic resonance imaging (MRI). The results show remarkable variation in response to HF/HS feeding from no change to more than a 600 percent change in body fat percentage after 8 weeks. Changes in body fat were highly heritable (>70%) and genetic mapping identified over a dozen genome-wide significant loci associated with changes in body fat after HF/HS feeding. A number of loci contained genes with previously described roles in obesity and genes identified in human GWAS studies for obesity, such as Npc1, Negr1, and Lyplal1. After HF/HS feeding several strains demonstrated signs of metabolic disease, such as hyperinsulnemia, hyperglycemia, and fatty liver disease, suggesting some strains may be prone to metabolic diseases after HF/HS feeding. Ongoing, integration of multiple high-throughput data sets, such as transcriptomic and metabolomic will allow for comprehensive analysis of dietary interactions contributing to obesity across multiple scales of biology and has the potential to greatly enhance our understanding of obesity and associated diseases.