Human Obese Gene Expression: Adipocyte-Specific Expression and Regional Differences in the Adipose Tissue
Human Obese Gene Expression: Adipocyte-Specific Expression and Regional Differences in the Adipose Tissue
复制标题
人类肥胖基因表达：脂肪组织中脂肪细胞特异性表达和区域差异
作者：
H. Masuzaki;Yoshihiro Ogawa;N. Isse;N. Satoh;T. Okazaki;M. Shigemoto;K. Mori;N. Tamura;K. Hosoda;Y. Yoshimasa;Hisato Jingami;Teruo Kawada;K. Nakao
肥胖基因（ob）的突变导致小鼠严重的遗传性肥胖和糖尿病，最近通过定位克隆分离。在这项研究中，我们分离了一个全长的人ob互补DNA （cDNA）克隆，并检测了ob基因在人体内的组织表达分布。人ob cDNA编码区的核苷酸序列与小鼠和大鼠ob cDNA编码区的核苷酸序列相同83%。对推导出的氨基酸序列分析表明，人ob蛋白是一个含有166个氨基酸的多肽，具有一个假定的信号序列，与小鼠和大鼠ob蛋白的同源性分别为84%和83%。利用克隆的人ob cDNA片段作为探针进行Northern blot分析，鉴定出一个大小为4.5 kb的单一信使RNA (mRNA)，在皮下、大网膜、腹膜后、淋巴周围和肠系膜脂肪垫的脂肪组织中大量存在。然而，在脑、心、肺、肝、胃、胰腺、脾、小肠、肾、前列腺、睾丸、结肠和骨骼肌中没有明显的ob mRNA。即使在同一个体中，脂肪组织中ob mRNA水平也因地区而异。此外，在人类脂肪组织中，ob基因表达发生在成熟的脂肪细胞中，而不是在基质血管细胞中。本研究首次报道了ob基因在人体组织中的表达，从而更好地理解了ob基因的生理和临床意义。
The obese (ob) gene, the mutation of which results in severe hereditary obesity and diabetes in mice, has recently been isolated through positional cloning. In this study, we isolated a full-length human ob complementary DNA (cDNA) clone and examined the tissue distribution of ob gene expression in humans. The nucleotide sequences of the human ob cDNA coding region were 83% identical to those of the mouse and rat ob cDNA coding regions. Analysis of the deduced amino acid sequences revealed that the human ob protein is a 166–amino acid polypeptide with a putative signal sequence and is 84 and 83% homologous to the mouse and rat ob proteins, respectively. Northern blot analysis using the cloned human ob cDNA fragment as a probe identified a single messenger RNA (mRNA) species 4.5 kb in size found abundantly in the adipose tissues obtained from the subcutaneous, omental, retroperitoneal, perilymphatic, and mesenteric fat pads. However, no significant amount of ob mRNA was present in the brain, heart, lung, liver, stomach, pancreas, spleen, small intestine, kidney, prostate, testis, colon, or skeletal muscle. The ob mRNA level in the adipose tissue varied from region to region even in the same individual. Furthermore, in the human adipose tissue, ob gene expression occurred in mature adipocytes rather than in stromal-vascular cells. This study is the first report of the elucidation of ob gene expression in human tissues, thereby leading to better understanding of the physiological and clinical implications of the ob gene.