Expression of the Bitter Taste Receptor, T2R38, in Enteroendocrine Cells of the Colonic Mucosa of Overweight/Obese vs. Lean Subjects.
Expression of the Bitter Taste Receptor, T2R38, in Enteroendocrine Cells of the Colonic Mucosa of Overweight/Obese vs. Lean Subjects.
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DOI：
10.1371/journal.pone.0147468
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Sternini C
中科院分区：
文献类型：
--
作者：
Latorre R;Huynh J;Mazzoni M;Gupta A;Bonora E;Clavenzani P;Chang L;Mayer EA;De Giorgio R;Sternini C
苦味受体(T2Rs)在哺乳动物胃肠道粘膜中表达。在小鼠结肠中，T2R138定位于肠内分泌细胞，并被长期高脂饮食上调，从而导致肥胖。本研究的目的是检测超重/肥胖(OW/OB)受试者与正常体重(NW)受试者相比，T2R38的表达是否发生变化，并鉴定T2R38(人的小鼠T2R138的对应物)在人结肠中的表达类型。35例健康受试者(20例OW/OB和15例NW)在结肠镜检查中获得结肠粘膜活检组织，并用T2R38、嗜铬粒素A(CGA)、胰高血糖素样肽-1(GLP-1)、胆囊收缩素(CCK)或YY肽(PYY)的抗体进行定量RT-PCR和免疫组织化学染色。OW/OB组大鼠结肠粘膜T2R38mRNA表达水平较NW组升高2倍，但差异无统计学意义(P=0.06)。OW/OB组T2R38免疫反应阳性细胞数显著高于正常对照组(P=0.7557)，且与BMI值呈显著正相关(r=0.7557；P=0.001)。在OW/OB和NW个体中，所有的T2R38-IR细胞都含有CGA-IR，支持它们是内分泌细胞。在两组中，T2R38-IR与CCK-、GLP1-或PYY-IR共存。OW/OB和NW个体的CGA-IR细胞总数相当。这项研究表明，T2R38在人类结肠粘膜中的不同肠内分泌细胞群中表达，并支持OW/OB患者T2R38的上调。T2R38可能介导了宿主对肥胖时能量平衡增加和腔内变化的功能反应，这可能涉及肠内分泌细胞释放多肽。
Bitter taste receptors (T2Rs) are expressed in the mammalian gastrointestinal mucosa. In the mouse colon, T2R138 is localized to enteroendocrine cells and is upregulated by long-term high fat diet that induces obesity. The aims of this study were to test whether T2R38 expression is altered in overweight/obese (OW/OB) compared to normal weight (NW) subjects and characterize the cell types expressing T2R38, the human counterpart of mouse T2R138, in human colon. Colonic mucosal biopsies were obtained during colonoscopy from 35 healthy subjects (20 OW/OB and 15 NW) and processed for quantitative RT-PCR and immunohistochemistry using antibodies to T2R38, chromogranin A (CgA), glucagon like peptide-1 (GLP-1), cholecystokinin (CCK), or peptide YY (PYY). T2R38 mRNA levels in the colonic mucosa of OW/OB were increased (> 2 fold) compared to NW subjects but did not reach statistical significance (P = 0.06). However, the number of T2R38 immunoreactive (IR) cells was significantly increased in OW/OB vs. NW subjects (P = 0.01) and was significantly correlated with BMI values (r = 0.7557; P = 0.001). In both OW/OB and NW individuals, all T2R38-IR cells contained CgA-IR supporting they are enteroendocrine. In both groups, T2R38-IR colocalized with CCK-, GLP1- or PYY-IR. The overall CgA-IR cell population was comparable in OW/OB and NW individuals. This study shows that T2R38 is expressed in distinct populations of enteroendocrine cells in the human colonic mucosa and supports T2R38 upregulation in OW/OB subjects. T2R38 might mediate host functional responses to increased energy balance and intraluminal changes occurring in obesity, which could involve peptide release from enteroendocrine cells.