Effects of the gut microbiota on host adiposity are modulated by the short-chain fatty-acid binding G protein-coupled receptor, Gpr41
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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DOI：
10.1073/pnas.0808567105
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发表时间：
2008-10-28
影响因子：
11.1
通讯作者：
Gordon, Jeffrey I.
中科院分区：
文献类型：
--
作者：
Samuel, Buck S.;Shaito, Abdullah;Gordon, Jeffrey I.
人类肠道的远端有数万亿的微生物，使我们能够从其他难以消化的膳食多糖中提取热量。多糖发酵的产物包括短链脂肪酸，其是Gpr 41的配体，Gpr 41是由肠上皮中的肠内分泌细胞亚群表达的G蛋白偶联受体。为了研究Gpr 41对能量平衡的贡献，我们比较了Gpr 41-/-和Gpr 41 +/+小鼠，这些小鼠要么是用完整的肠道微生物群常规饲养的，要么是无菌饲养的，然后作为年轻的成年人与人类远端肠道微生物群落的两个突出成员共同定植：糖分解细菌，多形拟杆菌和产甲烷古菌，史氏甲烷短杆菌。常规饲养的和用模型发酵群落定殖的无菌Gpr 41-/-小鼠都比它们的WT（+/+）同窝出生的小鼠显著更瘦并且体重更轻，尽管食物消耗水平相似。当比较无菌WT和无菌Gpr 41敲除动物时，这些差异并不明显。对无菌和共定植Gpr 41-/-和+/+同窝仔的功能基因组、生物化学和生理学研究表明，Gpr 41缺乏与PYY表达减少有关，PYY是一种肠内分泌细胞衍生的激素，通常抑制肠道运动、增加肠道转运率和减少从饮食中获得能量（短链脂肪酸）。这些结果表明，Gpr 41是宿主能量平衡的调节剂，其作用依赖于肠道微生物群。
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.