Overexpression of a short human seipin/BSCL2 isoform in mouse adipose tissue results in mild lipodystrophy
Overexpression of a short human seipin/BSCL2 isoform in mouse adipose tissue results in mild lipodystrophy
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小鼠脂肪组织中短人类 seipin/BSCL2 亚型的过度表达导致轻度脂肪营养不良
DOI：
10.1152/ajpendo.00237.2011
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发表时间：
2012-03-01
影响因子：
5.1
通讯作者：
Yang, Hongyuan
中科院分区：
文献类型：
--
作者：
Cui, Xin;Wang, Yuhui;Yang, Hongyuan
崔新，王永，孟立，费伟，邓杰，徐刚，彭新，鞠S，张立，刘刚，赵立，杨华.在小鼠脂肪组织中过表达短的人seipin/BSCL 2同种型导致轻度脂肪营养不良。Am J Physiol Endocrinol Metab 302：E705-E713，2012。首次发布于2012年1月10日; doi：10.1152/ajpendo.00237.2011。- Berardinelli-Seip先天性脂肪营养不良2型（BSCL 2）是一种隐性疾病，其特征是脂肪组织几乎完全丧失、胰岛素抵抗和脂肪肝。BSCL 2是由BSCL 2/seipin基因（编码seipin）的功能缺失突变引起的。最近已经在体外和体内确定了seipin在脂肪形成中的重要作用。然而，seipin在脂肪细胞发育的后期高度上调，其在成熟脂肪细胞中的作用仍有待阐明。因此，我们使用脂肪细胞特异性aP 2启动子产生过表达人BSCL 2基因的短同种型（编码398个氨基酸）的转基因小鼠。在白色脂肪组织中，转基因小鼠产生的seipin比同窝对照小鼠多150%。令人惊讶的是，seipin表达的增加显著降低了白色脂肪组织的质量以及脂肪细胞和脂滴的大小。这可能部分是由于转基因小鼠中脂肪分解速率升高。此外，转基因肝脏的三酰甘油含量增加了近50%。这些结果表明，seipin促进前脂肪细胞的分化，但可能会抑制成熟脂肪细胞中的脂质储存。
Cui X, Wang Y, Meng L, Fei W, Deng J, Xu G, Peng X, Ju S, Zhang L, Liu G, Zhao L, Yang H. Overexpression of a short human seipin/BSCL2 isoform in mouse adipose tissue results in mild lipodystrophy. Am J Physiol Endocrinol Metab 302: E705-E713, 2012. First published January 10, 2012; doi:10.1152/ajpendo.00237.2011.-Berardinelli-Seip congenital lipodystrophy type 2 (BSCL2) is a recessive disorder characterized by an almost complete loss of adipose tissue, insulin resistance, and fatty liver. BSCL2 is caused by loss-of-function mutations in the BSCL2/seipin gene, which encodes seipin. The essential role for seipin in adipogenesis has recently been established both in vitro and in vivo. However, seipin is highly upregulated at later stages of adipocyte development, and its role in mature adipocytes remains to be elucidated. We therefore generated transgenic mice overexpressing a short isoform of human BSCL2 gene (encoding 398 amino acids) using the adipocyte-specific aP2 promoter. The transgenic mice produced similar to 150% more seipin than littermate controls in white adipose tissue. Surprisingly, the increased expression of seipin markedly reduced the mass of white adipose tissue and the size of adipocytes and lipid droplets. This may be due in part to elevated lipolysis rates in the transgenic mice. Moreover, there was a nearly 50% increase in the triacylglycerol content of transgenic liver. These results suggest that seipin promotes the differentiation of preadipocytes but may inhibit lipid storage in mature adipocytes.