A critical evaluation of the putative role of C3adesArg (ASP) in lipid metabolism and hyperapobetalipoproteinemia.
A critical evaluation of the putative role of C3adesArg (ASP) in lipid metabolism and hyperapobetalipoproteinemia.
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DOI：
10.1016/s0161-5890(99)00108-x
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发表时间：
1999-09
影响因子：
3.6
通讯作者：
J. Kildsgaard;Eva M Zsigmond;Lawrence Chan;Rick A. Wetsel
中科院分区：
文献类型：
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作者：
J. Kildsgaard;Eva M Zsigmond;Lawrence Chan;Rick A. Wetsel
促酰化蛋白ASP是一种小的碱性血清蛋白，能够刺激培养成纤维细胞和脂肪细胞中甘油三酯的合成。ASP的序列分析表明，ASP与补体过敏毒素肽C3a的无活性片段C3adesArg相同。C3adesArg （ASP）可由成熟脂肪细胞分泌补体蛋白C3、补体因子B和补体因子D（脂肪素）三种补体蛋白产生。也有迹象表明，脂肪细胞可能表达一种特定的C3adesArg （ASP）受体，与最近克隆的c3a受体不同。这表明C3adesArg （ASP）作为脂肪细胞的自分泌，在脂肪组织的代谢中起核心作用。基于这些观察结果，提出了一种关于高载脂蛋白血症（hyperapoB）病因的假说。高载脂蛋白血症（hyperapoB）是一种家族性脂蛋白疾病，其特征是肝脏极低密度脂蛋白（VLDL）和低密度脂蛋白（LDL）颗粒分泌增加。如果C3adesArg （ASP）在脂肪组织中的功能受损，那么甘油三酯合成速率将随之降低，从而增加脂肪酸到肝脏的通量。作为对脂肪酸流量增加的反应，肝脏将增加其VLDL颗粒的产生，从而产生高载脂蛋白b的表型。这篇综述根据体外和体内收集的数据，批判性地评估了这一假设以及C3adesArg （ASP）作为甘油三酯合成的主要决定因素的潜在作用。
The acylation stimulating protein, ASP is a small, basic serum protein capable of stimulating triglyceride synthesis in cultured fibroblasts and adipocytes. Sequence analysis of ASP has shown that ASP is identical to C3adesArg — the inactive fragment of the complement anaphylatoxin peptide, C3a. It has been proposed that C3adesArg (ASP) can be generated by mature adipocytes secreting the three complement proteins: complement protein C3, factor B and factor D (adipsin). There have also been indications that adipocytes may express a specific C3adesArg (ASP)-receptor that is distinct from the recently cloned C3a-receptor. This suggests that C3adesArg (ASP) acts as an adipocyte autocrine and that it plays a central role in the metabolism of adipose tissue. Based on these observations a hypothesis for the etiology of hyperapobetalipoproteinemia (hyperapoB) has been proposed. Hyperapobetalipoproteinemia (hyperapoB), is a familial lipoprotein disorder characterized by increased hepatic secretion of very low density lipoprotein (VLDL) and low density lipoprotein (LDL) particles. If C3adesArg (ASP) function in the adipose tissue is impaired, a reduced rate of triglyceride synthesis will follow, generating an increased flux of fatty acids to the liver. In response to an increased flow of fatty acids, the liver will increase its production of VLDL particles yielding the phenotype of hyperapoB. This review critically assesses this hypothesis and the potential role of C3adesArg (ASP) as a major determinant for triglyceride synthesis in the light of data collected in vitro and in vivo.