title: Genetic control of obesity and gut microbiota composition in response to high-fat, high-sucrose diet in mice.
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.
authors: 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
authors: Brian W
authors: BW
authors: Parks
authors: Elizabeth
authors: E
authors: Nam
authors: Elin
authors: E
authors: Org
authors: Emrah
authors: E
authors: Kostem
authors: Frode
authors: F
authors: Norheim
authors: Simon T
authors: ST
authors: Hui
authors: Calvin
authors: C
authors: Pan
authors: Mete
authors: M
authors: Civelek
authors: Christoph D
authors: CD
authors: Rau
authors: Brian J
authors: BJ
authors: Bennett
authors: Margarete
authors: M
authors: Mehrabian
authors: Luke K
authors: LK
authors: Ursell
authors: Aiqing
authors: A
authors: He
authors: Lawrence W
authors: LW
authors: Castellani
authors: Bradley
authors: B
authors: Zinker
authors: Mark
authors: M
authors: Kirby
authors: Thomas A
authors: TA
authors: Drake
authors: Christian A
authors: CA
authors: Drevon
authors: Rob
authors: R
authors: Knight
authors: Peter
authors: P
authors: Gargalovic
authors: Todd
authors: T
authors: Kirchgessner
authors: Eleazar
authors: E
authors: Eskin
authors: Aldons J
authors: AJ
authors: Lusis
mesh_terms: D000818:Animals; D001823:Body Composition; D059305:Diet, High-Fat; D004040:Dietary Carbohydrates; D016678:Genome; D055106:Genome-Wide Association Study; D006801:Humans; D007413:Intestinal Mucosa / Q000382:microbiology*; D054892:Metagenome; D051379:Mice; D009765:Obesity / Q000235:genetics* / Q000473:pathology; D040641:Quantitative Trait Loci
chemical_list: D004040:Dietary Carbohydrates