Seipin ablation in mice results in severe generalized lipodystrophy
Seipin ablation in mice results in severe generalized lipodystrophy
复制标题
小鼠的 Seipin 消融会导致严重的全身性脂肪营养不良。
DOI：
10.1093/hmg/ddr205
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发表时间：
2011-08-01
影响因子：
3.5
通讯作者：
Yang, Hongyuan
中科院分区：
文献类型：
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作者：
Cui, Xin;Wang, Yuhui;Yang, Hongyuan
Berardinelli-Seip先天性脂肪营养不良2型（BSCL 2）是一种常染色体隐性遗传疾病，其特征是脂肪组织几乎完全丧失、胰岛素抵抗和脂肪肝。在这里，我们通过靶向破坏BSCL 2的致病基因seipin，创建了第一个BSCL 2小鼠模型。与其野生型同窝出生的小鼠相比，seipin（-/-）小鼠存活且体重正常，但显示脂肪组织质量、肝脂肪变性、葡萄糖耐受不良和高胰岛素血症显著减少。瘦素和脂联素的水平在seipin（-/-）小鼠中均显著降低，禁食后非酯化脂肪酸也是如此。然而，令人惊讶的是，在人BSCL中常见的高胆固醇血症在seipin（-/-）小鼠中没有观察到。我们的研究结果表明，可能的组织自主作用的seipin在肝脏脂质储存。seipin（-/-）小鼠的可用性应有助于阐明seipin的分子功能，并导致更好地理解人类BSCL 2的许多代谢后果。
Berardinelli-Seip congenital lipodystrophy type 2 (BSCL2) is an autosomal recessive disorder characterized by an almost complete loss of adipose tissue, insulin resistance and fatty liver. Here, we create the first murine model of BSCL2 by targeted disruption of seipin, the causative gene for BSCL2. Compared with their wild-type littermates, the seipin(-/-) mice are viable and of normal weight but display significantly reduced adipose tissue mass, hepatic steatosis, glucose intolerance and hyperinsulinemia. The levels of leptin and adiponectin were both significantly decreased in seipin(-/-) mice, so were non-esterified fatty acids upon fasting. Surprisingly, however, hypertriglyceridemia which is common in human BSCL, was not observed in seipin(-/-) mice. Our findings suggest a possible tissue-autonomous role of seipin in liver lipid storage. The availability of the seipin(-/-) mice should help elucidate the molecular function of seipin and lead to a better understanding of the many metabolic consequences of human BSCL2.