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Cell Metab. 2013 Jan 8;17(1):141-52. doi: 10.1016/j.cmet.2012.12.007.

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

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1
Department of Medicine/Division of Cardiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA. bparks@mednet.ucla.edu

Abstract

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.

PMID:
23312289
PMCID:
PMC3545283
DOI:
10.1016/j.cmet.2012.12.007
[Indexed for MEDLINE]
Free PMC Article
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