Angptl3 regulates lipid metabolism in mice
Angptl3 regulates lipid metabolism in mice
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DOI：
10.1038/ng814
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发表时间：
2002-02-01
期刊：
影响因子：
30.8
通讯作者：
Furukawa, H
中科院分区：
文献类型：
--
作者：
Koishi, R;Ando, Y;Furukawa, H
KK肥胖小鼠为中度肥胖，血浆胰岛素(高胰岛素血症)、血糖(高血糖)和血脂(高脂血症)水平异常高。在一个菌株(KK/SAN)中，我们观察到异常低的血脂水平(低脂血症)。这种突变表型是隐性遗传的孟德尔性状。在这里，我们报告了低脂血症(4号染色体中部的低基因座)的定位，以及导致低脂血症的常染色体隐性突变的位置克隆。HiL1基因编码一种独特的血管生成素样脂蛋白调节剂，我们将其命名为Allm1。它与Angptl3编码的血管生成素样蛋白3相同，在人类中具有高度保守的对应物。在KK/SAN小鼠中过表达Angpl3或静脉注射纯化的蛋白可引起循环血脂水平的增加。在C57BL/6J正常小鼠中也观察到这种增加。综上所述，这些数据表明，Angptl3调节动物的脂肪代谢。
The KK obese mouse is moderately obese and has abnormally high levels of plasma insulin (hyperinsulinemia), glucose (hyperglycemia) and lipids (hyperlipidemia). In one strain (KK/San), we observed abnormally low plasma lipid levels (hypolipidemia). This mutant phenotype is inherited recessively as a mendelian trait. Here we report the mapping of the hypolipidemia (hypo locus to the middle of chromosome 4 and positional cloning of the autosomal recessive mutation responsible for the hypolipidemia. The hypl locus encodes a unique angiopoietin-like lipoprotein modulator, which we named Allm1. it is identical to angiopoietin-like protein 3, encoded by Angptl3, and has a highly conserved counterpart in humans. Overexpression of Angpl3 or intravenous injection of the purified protein in KK/San mice elicited an increase in circulating plasma lipid levels. This increase was also observed in C57BL/6J normal mice. Taken together, these data suggest that Angptl3 regulates lipid metabolism in animals.