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

نویسندگان

  • 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
چکیده

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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عنوان ژورنال:
  • Cell metabolism

دوره 17 1  شماره 

صفحات  -

تاریخ انتشار 2013