Bscl2, encoding seipin, is a gene with a transmembrane endoplasmic reticulum protein product. Seipin is associated with lipid droplet biogenesis and is crucial for adipose tissue homeostasis [1,3]. It is involved in pathways related to adipocyte differentiation, lipid droplet morphology, and cellular triglyceride lipolysis [1]. Genetic models, such as knockout mouse models, have been valuable in studying its function.

In Bscl2 -/- mice, severe lipodystrophy with only residual white and brown fat pads was observed, validating seipin's critical role in adipose tissue homeostasis. These mice also developed diabetes and severe hepatic steatosis, and treatment with thiazolidinediones increased adipose tissue mass and partially rescued metabolic complications, highlighting lipoatrophy as a major cause of the Berardinelli-Seip congenital lipodystrophy (BSCL) phenotype [1]. Mice with cardiomyocyte-specific deletion of Bscl2 (Bscl2cKO) developed systolic dysfunction with dilation, along with elevated adipose triglyceride lipase (ATGL) expression, increased fatty acid oxidation, and reduced cardiac lipid contents. Cardiac dysfunction in Bscl2cKO mice could be partially reversed by a fatty acid oxidation inhibitor or prevented by genetic abolishment of one ATGL allele or high-fat diet feeding [2]. In a murine model of Celia's encephalopathy (Bscl2Celia/Celia), around 12% of homozygous and 5.4% of heterozygous knock-in mice showed severe neurological symptoms, along with lipodystrophy and mild hepatic steatosis [4].

In conclusion, Bscl2 is essential for adipose tissue homeostasis, controlling cardiac lipid catabolism and contractile function. Gene knockout mouse models have been instrumental in revealing its role in diseases such as BSCL, cardiac dysfunction, and Celia's encephalopathy, providing insights into disease mechanisms and potential therapeutic targets.

References:

1. Dollet, Lucile, Magré, Jocelyne, Cariou, Bertrand, Prieur, Xavier. 2013. Function of seipin: new insights from Bscl2/seipin knockout mouse models. In Biochimie, 96, 166-72. doi:10.1016/j.biochi.2013.06.022. https://pubmed.ncbi.nlm.nih.gov/23831461/

2. Zhou, Hongyi, Li, Jie, Su, Huabo, Young, Martin E, Chen, Weiqin. . BSCL2/Seipin deficiency in hearts causes cardiac energy deficit and dysfunction via inducing excessive lipid catabolism. In Clinical and translational medicine, 12, e736. doi:10.1002/ctm2.736. https://pubmed.ncbi.nlm.nih.gov/35384404/

3. Filali-Mouncef, Yasmina, Hunter, Catherine, Roccio, Federica, Proikas-Cezanne, Tassula, Reggiori, Fulvio. 2021. The ménage à trois of autophagy, lipid droplets and liver disease. In Autophagy, 18, 50-72. doi:10.1080/15548627.2021.1895658. https://pubmed.ncbi.nlm.nih.gov/33794741/

4. Cobelo-Gómez, Silvia, Sánchez-Iglesias, Sofía, Rábano, Alberto, San Millán, Beatriz, Araújo-Vilar, David. 2023. A murine model of BSCL2-associated Celia's encephalopathy. In Neurobiology of disease, 187, 106300. doi:10.1016/j.nbd.2023.106300. https://pubmed.ncbi.nlm.nih.gov/37717662/