BSCL2/Seipin in Lipid Catabolism and Lipodystrophy

Abstract

Adipose tissue is the body’s largest endocrine organ that plays a major role in systemic energy homeostasis and thermoregulation. Mutations in BSCL2 (a.k.a. Seipin) gene underlie human type 2 Berardinelli‐Seip Congenital Lipodystrophy (BSCL2) disease with near absence of adipose tissue at birth and severe metabolic diseases. Global Bscl2−/− mice largely recapitulate human BSCL2 lipodystrophy with severe insulin resistance and organomegly. Seipin is known for its critical role in controlling lipid droplet (LD) assembly at the LD‐forming subdomain of the endoplasmic reticulum (ER), but its exact functional role has been enigmatic. Our laboratory has focused on elucidating the mechanisms through which Seipin regulates adipocyte differentiation thus lipodystrophy and its associated metabolic diseases. This presentation will focus on the role of Seipin in mediating cAMP/PKA signaling to regulate lipid catabolism in mature white adipose tissue (WAT) and during perinatal brown adipose tissue (BAT) development which exert profound effect on metabolic homeostasis and thermogenesis. We will also explore the role of Seipin as a key node that links ATGL‐mediated lipolysis to govern mitochondrial dynamics and function in WAT, BAT and heart. These findings will highlight novel roles for Seipin in cellular and organismal biology and its importance in human health.Support or Funding InformationThis work was supported by NIH grant 1R01HL132182‐01.