Document Detail


Effects of the gut microbiota on host adiposity are modulated by the short-chain fatty-acid binding G protein-coupled receptor, Gpr41.
MedLine Citation:
PMID:  18931303     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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-/- and Gpr41+/+ 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 smithii. Both conventionally-raised and gnotobiotic Gpr41-/- mice colonized with the model fermentative community are significantly leaner and weigh less than their WT (+/+) 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 +/+ 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.
Authors:
Buck S Samuel; Abdullah Shaito; Toshiyuki Motoike; Federico E Rey; Fredrik Backhed; Jill K Manchester; Robert E Hammer; S Clay Williams; Jan Crowley; Masashi Yanagisawa; Jeffrey I Gordon
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2008-10-17
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  105     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2008 Oct 
Date Detail:
Created Date:  2008-10-29     Completed Date:  2008-12-01     Revised Date:  2011-02-21    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  16767-72     Citation Subset:  IM    
Affiliation:
Center for Genome Sciences and Department of Medicine, Washington University School of Medicine, St. Louis, MO 63108, USA.
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MeSH Terms
Descriptor/Qualifier:
Adiposity*
Animals
Bacteroides
Energy Metabolism
Gastrointestinal Tract / microbiology*
Germ-Free Life
Humans
Methanobrevibacter
Mice
Mice, Knockout
Peptide YY / analysis
Receptors, G-Protein-Coupled / physiology*
Symbiosis
Grant Support
ID/Acronym/Agency:
DK30292/DK/NIDDK NIH HHS; DK70977/DK/NIDDK NIH HHS; P30 DK056341-07/DK/NIDDK NIH HHS; P30 DK056341-08/DK/NIDDK NIH HHS; //Howard Hughes Medical Institute
Chemical
Reg. No./Substance:
0/Gpr41 protein, mouse; 0/Receptors, G-Protein-Coupled; 106388-42-5/Peptide YY
Comments/Corrections

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