Seipin, adipogenesis and lipid droplets.

Seipin, the human Berardinelli-Seip congenital lipodystrophy 2 gene product, regulates adipocyte differentiation and lipid droplet (LD) formation. The molecular function of seipin, however, remains to be elucidated. Here we summarize recent advances in the investigation of congenital generalized lipodystrophies (CGLs) and the cellular dynamics of LDs. Increasing evidence suggests that phospholipids play a crucial role in some key forms of CGL and also in determining the size and distribution of LDs. We explore the hypothesis that seipin functions in the metabolism of phospholipids, and that seipin deficiency causes accumulation of lipid intermediates and/or alters membrane phospholipid profiles. These changes could lead to tissue-specific abnormalities upon seipin dysfunction, such as defective adipocyte development and clustered LDs in fibroblasts.