Role of Seipin in Human Diseases and Experimental Animal Models

Abstract

Seipin, a protein encoded by the Berardinelli-Seip congenital lipodystrophy type 2 (BSCL2) gene, is famous for its key role in the biogenesis of lipid droplets and type 2 congenital generalised lipodystrophy (CGL2). BSCL2 gene mutations result in genetic diseases including CGL2, progressive encephalopathy with or without lipodystrophy (also called Celia’s encephalopathy), and BSCL2-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 BSCL2 gene mutations, paralleled by animal studies including systemic or specific Bscl2 gene knockout, or Bscl2 gene overexpression. In various animal models representing diseases that are not related to Bscl2 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 BSCL2 gene mutations.

Adipose transplantation improves olfactory function and neurogenesis via PKCα-involved lipid metabolism in Seipin Knockout mice

“…Seipin is known as the critical regulator of lipid metabolism. Loss of function mutation of Seipin led to not only lipid dysregulation but also neurological de cits, and the latter attracted augmenting attention [7,20]. In this study, we found abnormal lipid accumulation in SVZ of KO mice, accompanied by elevated glycerophospholipid and DG contents, resulting in abnormal SVZ neurogenesis, as well as olfactory memory dysfunction.…”

“…BSCL2, the Seipin coding gene, de ciency is responsible for type 2 congenital generalized lipodystrophy (CGL2), a rare autosomal disorder. CGL2 is characterized by the absence of whole-body adipose tissue and metabolic disorders such as hepatic steatosis, insulin resistance (IR) and dyslipidemia [20]. Noteworthy, individuals with CGL2 have an increased prevalence of mild mental retardation, which is not usually observed in CGL1 [10,38].…”