[PDF][PDF] Genetic control of obesity and gut microbiota composition in response to high-fat, high-sucrose diet in mice

BW Parks, E Nam, E Org, E Kostem, F Norheim, ST Hui… - Cell metabolism, 2013 - cell.com
BW Parks, E Nam, E Org, E Kostem, F Norheim, ST Hui, C Pan, M Civelek, CD Rau
Cell metabolism, 2013cell.com
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 …
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.
cell.com