"Seipin mediates Perilipin-1 recruitment to lipid droplets to preserve human adipocyte identity".

ABSTRACT: Congenital generalized lipodystrophy type 2 (CGL2) is caused by mutations in the BSCL2 gene, which encodes the protein seipin. However, how seipin loss causes adipose tissue failure remains unclear. Using human adipocyte progenitor cells capable of robust differentiation in vitro and in vivo, we reveal two unexpected findings that redefine CGL2 pathogenesis. First, seipin is dispensable for lipid droplet biogenesis but essential for recruiting the major adipocyte scaffold protein Perilipin 1 (PLIN1) to the lipid droplet surface. Second, we discover that the integrity of the lipid droplet serves as an organelle to nucleus quality control checkpoint enforcing adipocyte identity. Without seipin-dependent PLIN1 recruitment, adipocytes exhibit enhanced lipolysis and ceramide accumulation

SUBMITTER: Zhong D 

PROVIDER: S-EPMC12642227 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature