A cysteine-rich adipose tissue-specific secretory factor inhibits adipocyte differentiation
A cysteine-rich adipose tissue-specific secretory factor inhibits adipocyte differentiation
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DOI：
10.1074/jbc.c100028200
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发表时间：
2001-04-06
影响因子：
4.8
通讯作者：
Sul, HS
中科院分区：
文献类型：
--
作者：
Kim, KH;Lee, K;Sul, HS
12.5 kDa 富含半胱氨酸的脂肪组织特异性分泌因子 (ADSF/抵抗素) 是一种富含丝氨酸和半胱氨酸残基的新型分泌蛋白，具有独特的半胱氨酸重复基序 CX12CX8CXCX3 CX10CXCXCX9CC。在各种鼠类白色脂肪组织（包括腹股沟和附睾脂肪）以及棕色脂肪组织中发现了编码该蛋白质的单个 0.8 kb mRNA，但在所检查的任何其他组织中均未发现。在大鼠脂肪组织中发现了两种大小分别为 1.4 和 0.8 kb 的 mRNA。序列分析表明，这是由于两个聚腺苷酸化信号，近端的序列 AATACA 与鼠类 AATAAA 存在单碱基错配，远端的共有序列 AATAAA。在3T3-L1和原代前脂肪细胞分化为脂肪细胞期间，mRNA水平显着增加。它在脂肪组织中的表达受到严格的营养和激素调节；禁食期间 mRNA 水平非常低，而当禁食小鼠接受高碳水化合物饮食时，mRNA 水平会增加 25 倍。链脲佐菌素糖尿病患者的脂肪组织中该值也非常低，并且在施用胰岛素后增加了 23 倍。用表达载体转染的COS细胞的条件培养基处理后，3T3-L1细胞向脂肪细胞的转化被抑制80%。受调节的表达模式表明该因子作为动物营养状态的脂肪传感器，并且对脂肪细胞分化的抑制作用暗示其作为脂肪生成的反馈调节剂的功能。
A 12.5-kDa cysteine-rich adipose tissue-specific secretory factor (ADSF/resistin) is a novel secreted protein rich in serine and cysteine residues with a unique cysteine repeat motif of CX12CX8CXCX3 CX10CXCXCX9CC. A single 0.8-kilobase mRNA coding for this protein was found in various murine white adipose tissues including inguinal and epididymal fats and also in brown adipose tissue but not in any other tissues examined. Two species of mRNAs with sizes of 1.4 and 0.8 kilobases were found in rat adipose tissue. Sequence analysis indicates that this is because of two polyadenylation signals, the proximal one with the sequence AATACA with a single base mismatch from murine AATAAA and the distal consensus sequence AATAAA. The mRNA level was markedly increased during 3T3-L1 and primary preadipocyte differentiation into adipocytes. Its expression in adipose tissue is under tight nutritional and hormonal regulation; the mRNA level was very low during fasting and increased 25-fold when fasted mice were refed a high carbohydrate diet. It was also very low in adipose tissue of streptozotocin-diabetes and increased 23-fold upon insulin administration. Upon treatment with the conditioned medium from COS cells transfected with the expression vector, conversion of 3T3-L1 cells to adipocytes was inhibited by 80%. The regulated expression pattern suggesting this factor as an adipose sensor for the nutritional state of the animals and the inhibitory effect on adipocyte differentiation implicate its function as a feedback regulator of adipogenesis.