CLONING OF A PROTEIN THAT MEDIATES TRANSCRIPTIONAL EFFECTS OF FATTY-ACIDS IN PREADIPOCYTES - HOMOLOGY TO PEROXISOME PROLIFERATOR-ACTIVATED RECEPTORS
CLONING OF A PROTEIN THAT MEDIATES TRANSCRIPTIONAL EFFECTS OF FATTY-ACIDS IN PREADIPOCYTES - HOMOLOGY TO PEROXISOME PROLIFERATOR-ACTIVATED RECEPTORS
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DOI：
10.1074/jbc.270.5.2367
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发表时间：
1995-02-03
影响因子：
4.8
通讯作者：
GRIMALDI, PA
中科院分区：
文献类型：
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作者：
AMRI, EZ;BONINO, F;GRIMALDI, PA
前脂肪细胞暴露于长链脂肪酸诱导脂肪细胞分化的几个基因标记物的表达。本报告描述了克隆，从前脂肪细胞库，编码脂肪酸激活受体，FAAR的cDNA。该cDNA具有核激素受体的特征和配体结合结构域，编码一个440个氨基酸的过氧化物酶体增殖物激活受体（PPAR）相关蛋白。推导的蛋白质序列与从人骨肉瘤细胞分离的hNUC I的蛋白质序列同源性为88%，FAAR mRNA在脂肪组织、肠、脑、心脏和骨骼肌中丰富，而在肾、肝、睾丸和脾中较少。该mRNA在生长中的Ob 1771和3 T3-F442 A前脂肪细胞中检测不到，在分化早期被强烈诱导，并且被脂肪酸增加，使用杂合受体的转录测定显示脂肪酸的强刺激和贝特类的弱诱导。用FAAR表达载体转染3 T3-C2成纤维细胞，赋予脂肪细胞脂质结合蛋白和脂肪酸转运蛋白的脂肪酸诱导。这些基因的转录诱导表现出与前脂肪细胞中所描述的相同的诱导剂特异性。数据表明FAAR可能是前脂肪细胞中脂肪酸转录作用的介体。
Exposure of preadipocytes to long chain fatty acids induces expression of several gene markers of adipocyte differentiation. This report describes the cloning, from a preadipocyte library, of a cDNA encoding a fatty acid-activated receptor, FAAR. The cDNA had the characteristics and ligand-binding domains of nuclear hormone receptors and encoded a 440 amino acid protein related to peroxisome proliferator-activated receptors, PPAR. The deduced protein sequence was 88% homologous to that of hNUC I, isolated from human osteosarcoma cells, FAAR mRNA was abundant in adipose tissue, intestine, brain, heart, and skeletal muscles and less abundant in kidney, liver, testis, and spleen, The mRNA was undetectable in growing Ob1771 and 3T3-F442A preadipocytes, was strongly induced early during differentiation, and was increased by fatty acid, Transcription assays using hybrid receptor showed strong stimulation by fatty acid and weaker induction by fibrates, Transfection of 3T3-C2 fibroblasts, with a FAAR expression vector, conferred fatty acid inducibility of the adipocyte lipid-binding protein and the fatty acid transporter, Transcriptional induction of these genes exhibited inducer specificity identical to that described in preadipocytes, In summary, the data indicate that FAAR is likely a mediator of fatty acid transcriptional effects in preadipocytes.