Leptin and the obesity receptor (OB-R) in the small intestine and colon: A colocalization study

Leptin and the obesity receptor (OB-R) in the small intestine and colon: A colocalization study
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DOI:
10.1369/jhc.2008.950782
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发表时间:
2008-07-01
影响因子:
3.2
通讯作者:
Danielsen, E. Michael
Danielsen, E. Michael
中科院分区:
生物学3区
文献类型:
--
作者:
Hansen, Gert H.;Niels-Christiansen, Lise-Lotte;Danielsen, E. Michael

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瘦素是一种在机体整体能量稳态中发挥重要作用的激素,肥胖受体C)B-R广泛分布于机体内。在肠道中,瘦素有多种作用,但目前尚不清楚该激素通过内分泌或外分泌信号通路在多大程度上影响肠上皮细胞。为了阐明这一点,研究了内源性猪瘦素和 C)B-R 在肠细胞和结肠细胞中的定位。免疫荧光显微镜观察发现,瘦素和OB-R主要存在于肠细胞和结肠细胞的基底外侧膜中,也存在于细胞的顶微绒毛膜中。通过电子显微镜,在上皮细胞的基底外侧表面经常检测到质膜中激素和受体的共聚以及内体中的定位,这表明瘦素信号传导活性。相反,共簇在顶端细胞表面发生的频率较低,并且几乎检测不到顶端下内体定位。我们得出的结论是,肠上皮细胞中的瘦素作用发生在基底外侧质膜上,表明该激素在空肠和结肠中均使用内分泌途径。相反,获得的数据没有提供肠道内激素的外分泌、腔内作用的证据。
Leptin is a hormone that plays an important role in overall body energy homeostasis, and the obesity receptor, C)B-R, is widely distributed in the organism. In the intestine, a multitude of leptin actions have been reported, but it is currently unclear to what extent the hormone affects the intestinal epithelial cells by an endocrine or exocrine signaling pathway. To elucidate this, the localization of endogenous porcine leptin and C)B-R in enterocytes and colonocytes was studied. By immunofluorescence microscopy, both leptin and OB-R were mainly observed in the basolateral membrane of enterocytes and colonocytes but also in the apical microvillar membrane of the cells. By electron microscopy, coclustering of hormone and receptor in the plasma membrane and localization in endosomes was frequently detected at the basolateral surface of the epithelial cells, indicative of leptin signaling activity. In contrast, coclustering occurred less frequently at the apical cell surface, and subapical endosomal localization was hardly detectable. We conclude that leptin action in intestinal epithelial cells takes place at the basolateral plasma membrane, indicating that the hormone uses an endocrine pathway both in the jejunum and colon. In contrast, the data obtained did not provide evidence for an exocrine, lumenal action of the hormone in the intestine.