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

Authors :
Parks BW
Nam E
Org E
Kostem E
Norheim F
Hui ST
Pan C
Civelek M
Rau CD
Bennett BJ
Mehrabian M
Ursell LK
He A
Castellani LW
Zinker B
Kirby M
Drake TA
Drevon CA
Knight R
Gargalovic P
Kirchgessner T
Eskin E
Lusis AJ
Source :
Cell metabolism [Cell Metab] 2013 Jan 08; Vol. 17 (1), pp. 141-52.
Publication Year :
2013

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.<br /> (Copyright © 2013 Elsevier Inc. All rights reserved.)

Details

Language :
English
ISSN :
1932-7420
Volume :
17
Issue :
1
Database :
MEDLINE
Journal :
Cell metabolism
Publication Type :
Academic Journal
Accession number :
23312289
Full Text :
https://doi.org/10.1016/j.cmet.2012.12.007