Identification of adipocyte adhesion molecule (ACAM), a novel CTX gene family, implicated in adipocyte maturation and development of obesity
Identification of adipocyte adhesion molecule (ACAM), a novel CTX gene family, implicated in adipocyte maturation and development of obesity
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DOI：
10.1042/bj20041709
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发表时间：
2005-04-15
影响因子：
4.1
通讯作者：
Makino, H
中科院分区：
文献类型：
--
作者：
Eguchi, J;Wada, J;Makino, H
很少有细胞粘附分子在成熟脂肪细胞中表达的报道，细胞粘附过程在脂肪细胞生物学中的意义也不清楚。在本研究中，我们确定了ACAM（脂肪细胞粘附分子），一个新的同源的CTX（皮质胸腺细胞标记在爪蟾）基因家族。在基于PCR的cDNA消减过程中分离ACAM cDNA，并且其mRNA显示在OLETF（大冢长埃文斯德岛脂肪）大鼠（II型糖尿病和肥胖的动物模型）的WAT（白色脂肪组织）中上调。ACAM由372个氨基酸组成，具有信号肽、V型（可变）和C2型（恒定）IG结构域、单个跨膜片段和胞质尾区。大鼠的氨基酸序列与小鼠（94%）和人（87%）高度同源。ACAM mRNA主要表达在OLETF大鼠的WATS中，并且随着肥胖的发展而增加，直到30周龄，这是体重达到峰值的时候。Western blot分析显示，ACAM蛋白，约。45 kDa，与从OLETF大鼠肠系膜和皮下脂肪沉积物分离的成熟脂肪细胞的质膜组分相关。在遗传性肥胖db/db小鼠、饮食诱导的肥胖ICR小鼠和人类肥胖受试者的WAT中也显示了肥胖中ACAM mRNA的上调。在原代培养的小鼠和人脂肪细胞中，ACAM mRNA表达在分化过程中进行性上调。建立了稳定转染的中国仓鼠卵巢K1细胞系，ACAM mRNA定量和细胞聚集实验表明，嗜同性聚集程度与ACAM mRNA表达密切相关。总之，ACAM可能是脂肪细胞分化和肥胖发生的关键粘附分子。
Few cell adhesion molecules have been reported to be expressed in mature adipocytes, and the significance of cell adhesion process in adipocyte biology is also unknown. In the present study, we identified ACAM (adipocyte adhesion molecule), a novel homologue of the CTX (cortical thymocyte marker in Xenopus) gene family. ACAM cDNA was isolated during PCR-based cDNA subtraction, and its mRNA was shown to be up-regulated in WATs (white adipose tissues) of OLETF (Otsuka Long-Evans Tokushima fatty) rats, an animal model for Type II diabetes and obesity. ACAM, 372 amino acids in total, has a signal peptide, V-type (variable) and C2-type (constant) Ig domains, a single transmembrane segment and a cytoplasmic tail. The amino acid sequence in rat is highly homologous to mouse (94%) and human (87%). ACAM mRNA was predominantly expressed in WATs in OLETF rats, and increased with the development of obesity until 30 weeks of age, which is when the peak of body mass is reached. Western blot analysis revealed that ACAM protein, approx. 45 kDa, was associated with plasma membrane fractions of mature adipocytes isolated from mesenteric and subdermal adipose deposits of OLETF rats. Up-regulation of ACAM mRNAs in obesity was also shown in WATs of genetically obese db/db mice, diet-induced obese ICR mice and human obese subjects. In primary cultured mouse and human adipocytes, ACAM mRNA expression was progressively up-regulated during differentiation. Several stably transfected Chinese-hamster ovary K1 cell lines were established, and the quantification of ACAM mRNA and cell aggregation assay revealed that the degree of homophilic aggregation correlated well with ACAM mRNA expression. In summary, ACAM may be the critical adhesion molecule in adipocyte differentiation and development of obesity.