Recent advances in gut nutrient chemosensing.
Recent advances in gut nutrient chemosensing.
复制标题
DOI：
10.2174/092986712803414033
复制
发表时间：
2012
影响因子：
4.1
通讯作者：
Kaunitz JD
中科院分区：
文献类型：
--
作者：
Nguyen CA;Akiba Y;Kaunitz JD
肠道营养化学传感领域正在迅速发展。最近的进展揭示了特定营养成分引起多种代谢反应的机制。肠道中G蛋白偶联受体（GPCR）的去磷酸化有助于识别以前未配体的受体及其同源配体。在这篇综述中，我们讨论了营养受体，它们的配体偏好，和诱发的神经激素反应。家族A GPCR包括感受蛋白质和蛋白水解降解产物的受体GPR 93和游离脂肪酸感受受体。短链游离脂肪酸是FFA 2（以前称为GPR 43）和FFA 3（以前称为GPR 41）的配体。FFA 1，以前称为GPR 40，由长链脂肪酸激活，GPR 120由中链和长链脂肪酸激活。还鉴定了GPR 119激动剂乙醇酰胺油酰乙醇酰胺（OEA）和胆汁酸GPR 131激动剂。家族C受体配体偏好包括L-氨基酸、碳水化合物和促味剂。代谢型谷氨酸受体（mGluR）、钙敏感受体（CaR）和GPCR家族C、组6、亚型A受体（GPRC 6A）介导L-氨基酸敏感。味觉受体在肠道化学传感中具有拟议的作用;甜、苦和鲜味通过GPCR在肠道中引起反应。碳水化合物感知的机制仍然存在争议：在L细胞中表达的异二聚体味觉受体T1 R2/T1 R3和钠葡萄糖协同转运蛋白1（SGLT-1）是两个主要的候选者。特异性营养素受体及其相应配体的鉴定可以为治疗糖尿病、酸反流、前肠粘膜损伤和肥胖提供新的治疗靶点。
The field of gut nutrient chemosensing is evolving rapidly. Recent advances have uncovered the mechanism by which specific nutrient components evoke multiple metabolic responses. Deorphanization of G protein-coupled receptors (GPCRs) in the gut has helped identify previously unliganded receptors and their cognate ligands. In this review, we discuss nutrient receptors, their ligand preferences, and the evoked neurohormonal responses. Family A GPCRs includes receptor GPR93, which senses protein and proteolytic degradation products, and free fatty acid-sensing receptors. Short-chain free fatty acids are ligands for FFA2, previously GPR43, and FFA3, previously GPR41. FFA1, previously GPR40, is activated by long-chain fatty acids with GPR120 activated by medium- and long-chain fatty acids. The GPR119 agonist ethanolamide oleoylethanolamide (OEA) and bile acid GPR131 agonists have also been identified. Family C receptors ligand preferences include L-amino acids, carbohydrate, and tastants. The metabotropic glutamate receptor (mGluR), calcium-sensing receptor (CaR), and GPCR family C, group 6, subtype A receptor (GPRC6A) mediate L-amino acid-sensing. Taste receptors have a proposed role in intestinal chemosensing; sweet, bitter, and umami evoke responses in the gut via GPCRs. The mechanism of carbohydrate-sensing remains controversial: the heterodimeric taste receptor T1R2/T1R3 and sodium glucose cotransporter 1 (SGLT-1) expressed in L cells are the two leading candidates. Identification of specific nutrient receptors and their respective ligands can provide novel therapeutic targets for the treatment of diabetes, acid reflux, foregut mucosal injury, and obesity.