West China Pancreatitis Centre, Centre for Integrated Traditional Chinese Medicine and Western Medicine, West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu 610041, China.
Department of Endocrinology and Metabolism, West China Hospital of Sichuan University, Chengdu 610041, China.
Biomolecules. 2022 Jun 17;12(6):840. doi: 10.3390/biom12060840.
Seipin, a protein encoded by the Berardinelli-Seip congenital lipodystrophy type 2 () gene, is famous for its key role in the biogenesis of lipid droplets and type 2 congenital generalised lipodystrophy (CGL2). gene mutations result in genetic diseases including CGL2, progressive encephalopathy with or without lipodystrophy (also called Celia's encephalopathy), and -associated motor neuron diseases. Abnormal expression of seipin has also been found in hepatic steatosis, neurodegenerative diseases, glioblastoma stroke, cardiac hypertrophy, and other diseases. In the current study, we comprehensively summarise phenotypes, underlying mechanisms, and treatment of human diseases caused by gene mutations, paralleled by animal studies including systemic or specific gene knockout, or gene overexpression. In various animal models representing diseases that are not related to mutations, differential expression patterns and functional roles of seipin are also described. Furthermore, we highlight the potential therapeutic approaches by targeting seipin or its upstream and downstream signalling pathways. Taken together, restoring adipose tissue function and targeting seipin-related pathways are effective strategies for CGL2 treatment. Meanwhile, seipin-related pathways are also considered to have potential therapeutic value in diseases that are not caused by gene mutations.
Seipin 是由 Berardinelli-Seip 先天性脂肪营养不良 2 型 () 基因突变编码的蛋白，其在脂滴的生物发生和 2 型先天性全身性脂肪营养不良 (CGL2) 中发挥关键作用而闻名。该基因突变导致包括 CGL2、伴有或不伴有脂肪营养不良的进行性脑病（也称为 Celia 脑病）和 -相关运动神经元疾病等遗传疾病。在肝脂肪变性、神经退行性疾病、胶质母细胞瘤中风、心脏肥大等疾病中也发现 seipin 异常表达。在本研究中，我们全面总结了由 基因突变引起的人类疾病的表型、潜在机制和治疗方法，并通过包括系统性或特异性 基因敲除或 基因过表达在内的动物研究进行了平行比较。在代表与 突变无关的疾病的各种动物模型中，还描述了 seipin 的差异表达模式和功能作用。此外，我们还强调了通过针对 seipin 或其上游和下游信号通路来治疗疾病的潜在方法。综上所述，恢复脂肪组织功能和靶向 seipin 相关途径是治疗 CGL2 的有效策略。同时，seipin 相关途径也被认为在非由 基因突变引起的疾病中具有潜在的治疗价值。
