Authors:
Brian W. Parks, Elizabeth Nam, Elin Org, Emrah Kostem, Frode Norheim, Simon T. Hui, Calvin Pan, Mete Civelek, Christoph D. Rau, Brian J. Bennett, Margarete Mehrabian, Luke K. Ursell, Aiqing He, Lawrence W. Castellani, Bradley Zinker, Mark Kirby, Thomas A. Drake, Christian A. Drevon, Rob Knight, Peter Gargalovic, Todd Kirchgessner, Eleazar Eskin, & Aldons J. Lusis
Summary:
Obesity is a highly heritable disease driven by complex interactions between genetic and environmental factors. Human genome-wide association studies (GWAS) have identified a number of loci contributing to obesity; however, a major limitation of these studies is the inability to assess environmental interactions common to obesity. Using a systems genetics approach, we measured obesity traits, global gene expression, and gut microbiota composition in response to a high-fat/high-sucrose (HF/HS) diet of more than 100 inbred strains of mice. Here we show that HF/HS feeding promotes robust, strain-specific changes in obesity that are not accounted for by food intake and provide evidence for a genetically determined set point for obesity. GWAS analysis identified 11 genome-wide significant loci associated with obesity traits, several of which overlap with loci identified in human studies. We also show strong relationships between genotype and gut microbiota plasticity during HF/HS feeding and identify gut microbial phylotypes associated with obesity.
Source:
Cell Metabolism; Vol. 17, Issue 1, 141-152 (01/08/13)