Genetic Control of Obesity and Gut Microbiota Composition in Response to High-fat, High-sucrose Diet in Mice

Overview

Journal Cell Metab

Publisher Cell Press

Specialties Cell Biology
Endocrinology

Date 2013 Jan 15

PMID 23312289

Citations 288

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

Affiliations

Soon will be listed here.

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.

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