1. Effects of the gut microbiota on host adiposity are modulated by the short-chain fatty-acid binding G protein-coupled receptor, Gpr41.
- Author
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Samuel, Buck S., Shaito, Abdullah, Motoike, Toshiyuki, Rey, Federico E., Backhed, Fredrik, Manchester, Jill K., Hammer, Robert E., Williams, S. Clay, Crowley, Jan, Yanagisawa, Masashi, and Gordon, Jeffrey I.
- Subjects
HOST-bacteria relationships ,POLYSACCHARIDES ,FERMENTATION ,FATTY acids ,G proteins ,LABORATORY mice ,GASTROINTESTINAL hormones - Abstract
The distal human intestine harbors trillions of microbes that allow us to extract calories from otherwise indigestible dietary polysaccharides. The products of polysaccharide fermentation include short-chain fatty acids that are ligands for Gpr41, a G protein-coupled receptor expressed by a subset of enteroendocrine cells in the gut epithelium. To examine the contribution of Gpr41 to energy balance, we compared Gpr41-I- and Gpr41+I+ mice that were either conventionally-raised with a complete gut microbiota or were reared germ-free and then cocolonized as young adults with two prominent members of the human distal gut microbial community: the saccharolytic bacterium, Bacteroides thetaiotaomicron and the methanogenic archaeon, Methanobrevibacter smithü. Both conventionally-raised and gnotobiotic Gpr41-/- mice colonized with the model fermentative community are significantly leaner and weigh less than their WT (+I+) littermates, despite similar levels of chow consumption. These differences are not evident when germ-free WT and germ-free Gpr41 knockout animals are compared. Functional genomic. biochemical, and physiologic studies of germ-free and cocolonized Gpr41-/- and +1+ littermates disclosed that Gpr41-deficiency is associated with reduced expression of PYY, an enteroendocrine cell-derived hormone that normally inhibits gut motility, increased intestinal transit rate, and reduced harvest of energy (short-chain fatty acids) from the diet. These results reveal that Gpr41 is a regulator of host energy balance through effects that are dependent upon the gut microbiota. [ABSTRACT FROM AUTHOR]
- Published
- 2008
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