| Effects of the gut microbiota on host adiposity are modulated by the short-chain fatty-acid binding G protein-coupled receptor, Gpr41. | |
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MedLine Citation:
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PMID: 18931303 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2008-10-17 |
Journal Detail:
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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:
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Created Date: 2008-10-29 Completed Date: 2008-12-01 Revised Date: 2011-02-21 |
Medline Journal Info:
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Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: United States |
Other Details:
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Languages: eng Pagination: 16767-72 Citation Subset: IM |
Affiliation:
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Center for Genome Sciences and Department of Medicine, Washington University School of Medicine, St. Louis, MO 63108, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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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:
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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:
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0/Gpr41 protein, mouse; 0/Receptors, G-Protein-Coupled; 106388-42-5/Peptide YY |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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