Enterochromaffin 5-HT cells - A major target for GLP-1 and gut microbial metabolites.
Enterochromaffin 5-HT cells - A major target for GLP-1 and gut microbial metabolites.
复制标题
肠粘蛋白5-HT细胞 - GLP-1和肠道微生物代谢产物的主要靶标。
DOI：
10.1016/j.molmet.2018.03.004
复制
发表时间：
2018-05
影响因子：
8.1
通讯作者：
Schwartz TW
中科院分区：
文献类型：
--
作者：
Lund ML;Egerod KL;Engelstoft MS;Dmytriyeva O;Theodorsson E;Patel BA;Schwartz TW
据信，储存5-HT的肠嗜铬（EC）细胞对营养物质和肠道微生物组分产生反应，并且表达5-HT受体的传入迷走神经元已被描述为胃肠道中营养物质的主要传感器。然而，EC细胞感知营养物质和肠道微生物群的分子机制仍不清楚。TPH 1，5-HT产生酶，嗜铬粒蛋白A，一种酸性蛋白质，负责分泌颗粒储存的5-HT，高度富集在FACS纯化的EC细胞从小肠和结肠使用5-HT抗体为基础的方法。令人惊讶的是，来自小肠的EC细胞不表达针对脂质和蛋白质代谢物的GPCR传感器，例如FFAR 1、GPR 119、GPBAR 1（TGR 5）、CaSR和GPR 142，这与邻近的储存GLP-1的肠内分泌细胞相反。然而，通过qPCR和使用受体抗体的免疫组织化学判断，GLP-1受体在EC细胞中特别高表达和富集。使用HPLC和特定安培法，GLP-1受体激动剂强烈刺激肠道制剂中的5-HT分泌。结肠EC细胞表达许多不同类型的已知的和潜在的微生物代谢物的GPCR传感器，包括SCFA的三种受体，即FFAR 2、OLF 78和OLF 558，以及芳香酸的受体，GPR 35;次级胆汁酸GPBAR 1;以及酰胺和乳酸盐，GPR 132。营养代谢物显然不直接刺激小肠EC细胞，而是通过旁分泌机制，涉及从邻近的肠内分泌细胞分泌的GLP-1。相比之下，结肠EC细胞能够感知肠道微生物群产生的多种不同代谢物以及肠道激素，包括GLP-1。通过基于抗体的FACS分选获得纯的肠5-HT细胞。小肠5-HT细胞不表达营养代谢物的传感器。结肠5-HT细胞表达多种类型的肠道微生物代谢物受体。GLP-1刺激5-HT从离体肠制备物释放。GLP-1和5-HT串联并协同作用以控制GI-道和代谢。
5-HT storing enterochromaffin (EC) cells are believed to respond to nutrient and gut microbial components, and 5-HT receptor-expressing afferent vagal neurons have been described to be the major sensors of nutrients in the GI-tract. However, the molecular mechanism through which EC cells sense nutrients and gut microbiota is still unclear. TPH1, the 5-HT generating enzyme, and chromogranin A, an acidic protein responsible for secretory granule storage of 5-HT, were highly enriched in FACS-purified EC cells from both small intestine and colon using a 5-HT antibody-based method. Surprisingly, EC cells from the small intestine did not express GPCR sensors for lipid and protein metabolites, such as FFAR1, GPR119, GPBAR1 (TGR5), CaSR, and GPR142, in contrast to the neighboring GLP-1 storing enteroendocrine cell. However, the GLP-1 receptor was particularly highly expressed and enriched in EC cells as judged both by qPCR and by immunohistochemistry using a receptor antibody. GLP-1 receptor agonists robustly stimulated 5-HT secretion from intestinal preparations using both HPLC and a specific amperometric method. Colonic EC cells expressed many different types of known and potential GPCR sensors of microbial metabolites including three receptors for SCFAs, i.e. FFAR2, OLF78, and OLF558 and receptors for aromatic acids, GPR35; secondary bile acids GPBAR1; and acyl-amides and lactate, GPR132. Nutrient metabolites apparently do not stimulate EC cells of the small intestine directly but through a paracrine mechanism involving GLP-1 secreted from neighboring enteroendocrine cells. In contrast, colonic EC cells are able to sense a multitude of different metabolites generated by the gut microbiota as well as gut hormones, including GLP-1. Pure intestinal 5-HT cells are obtained through antibody-based FACS sorting. Small intestinal 5-HT cells do not express sensors for nutrient metabolites. Colonic 5-HT cells express multiple types of receptors for gut microbial metabolites. GLP-1 stimulates 5-HT release from ex vivo intestinal preparations. GLP-1 and 5-HT act in series and synergy to control GI-tract and metabolism.
登录
查看更多内容
下丘脑胰高血糖素样肽1受体足够，但对于调节小鼠的能量平衡和葡萄糖稳态不需要。
影响因子：
7.7
作者：
Burmeister MA;Ayala JE;Smouse H;Landivar-Rocha A;Brown JD;Drucker DJ;Stoffers DA;Sandoval DA;Seeley RJ;Ayala JE
通讯作者：
Ayala JE
影响因子：
2.5
作者：
Christensen, Louise W.;Kuhre, Rune E.;Holst, Jens J.
通讯作者：
Holst, Jens J.
影响因子：
64.5
作者：
Bellono NW;Bayrer JR;Leitch DB;Castro J;Zhang C;O'Donnell TA;Brierley SM;Ingraham HA;Julius D
通讯作者：
Julius D
胆汁酸主要通过进入基底外侧G蛋白偶联的胆汁酸受体触发GLP-1。
影响因子：
4.8
作者：
Brighton CA;Rievaj J;Kuhre RE;Glass LL;Schoonjans K;Holst JJ;Gribble FM;Reimann F
通讯作者：
Reimann F
影响因子：
4.8
作者：
Egerod, Kristoffer L.;Engelstoft, Maja S.;Schwartz, Thue W.
通讯作者：
Schwartz, Thue W.