Prinz Philip, Goebel-Stengel Miriam, Teuffel Pauline, Rose Matthias, Klapp Burghard F, Stengel Andreas
Charité Center for Internal Medicine and Dermatology, Department for Psychosomatic Medicine, Charité-Universitätsmedizin Berlin, Hindenburgdamm 30, 12203 Berlin, Germany.
Department of Internal Medicine, Martin-Luther Krankenhaus, Caspar-Theyß-Str. 27-31, 14193 Berlin, Germany.
Biochem Biophys Res Commun. 2016 Feb 12;470(3):521-527. doi: 10.1016/j.bbrc.2016.01.113. Epub 2016 Jan 20.
Nesfatin-1 was recently identified and introduced as food intake-regulatory hormone. Soon thereafter, mounting evidence indicated a much broader role for nesfatin-1 with an involvement in the regulation of food intake, gastrointestinal motility, glucose homeostasis, blood pressure and stress. Despite the growing knowledge on the physiological regulation and functions of nesfatin-1, the receptor mediating these effects remains to be characterized. Therefore, the aim of this study was to investigate the peripheral and central localization of the nesfatin-1 receptor by autoradiography. Male Sprague-Dawley rats were used and peripheral as well as brain tissue was processed for (125)I-nesfatin-1 autoradiography. In peripheral tissues, an autoradiographic signal was observed in the gastric mucosa of corpus and antrum, in duodenum, jejunum and ileum, while no signal was detected in the colon. Preabsorption of (125)I-nesfatin-1 with non-labeled nesfatin-1 greatly diminished the autoradiographic signal in the stomach indicating specificity (-32%, p < 0.001). A displacement assay showed an effective concentration by which 50% of (125)I-nesfatin-1 bound to the receptor (EC50) in the gastric corpus of 80 pM. Moreover, autoradiography was observed in endocrine tissues including the pituitary, pancreas, adrenal gland, testis and visceral adipose tissue. In addition, also heart, skeletal muscle, lung, liver and kidney showed autoradiographic signals. In the brain, strong (125)I-nesfatin-1 autoradiography was detected in the cortex, paraventricular nucleus of the hypothalamus, area postrema, dorsal motor nucleus of the vagus nerve and cerebellum. Based on the distribution of nesfatin-1 autoradiography, nesfatin-1 is a pleiotropic hormone that is involved in the regulation of several homeostatic functions.
内脂素-1最近被鉴定并作为食物摄入调节激素引入。此后不久，越来越多的证据表明内脂素-1具有更广泛的作用，参与食物摄入、胃肠蠕动、葡萄糖稳态、血压和应激的调节。尽管对内脂素-1的生理调节和功能的认识不断增加，但介导这些作用的受体仍有待确定。因此，本研究的目的是通过放射自显影术研究内脂素-1受体的外周和中枢定位。使用雄性Sprague-Dawley大鼠，对其外周和脑组织进行（125）I-内脂素-1放射自显影术处理。在外周组织中，在胃体和胃窦的胃黏膜、十二指肠、空肠和回肠中观察到放射自显影信号，而在结肠中未检测到信号。用未标记的内脂素-1预吸收（125）I-内脂素-1可大大降低胃中的放射自显影信号，表明具有特异性（-32%，p<0.001）。置换试验显示，在胃体中，50%的（125）I-内脂素-1与受体结合的有效浓度（EC50）为80 pM。此外，在内分泌组织包括垂体、胰腺、肾上腺、睾丸和内脏脂肪组织中观察到放射自显影。此外，心脏、骨骼肌、肺、肝和肾也显示出放射自显影信号。在脑中，在皮质、下丘脑室旁核、最后区、迷走神经背运动核和小脑中检测到强烈的（125）I-内脂素-1放射自显影。基于内脂素-1放射自显影的分布，内脂素-1是一种多效性激素，参与多种稳态功能的调节。
