Seipin Deficiency as a Model of Severe Adipocyte Dysfunction: Lessons from Rodent Models and Teaching for Human Disease

Int J Mol Sci. 2022 Jan 11;23(2):740. doi: 10.3390/ijms23020740.


Obesity prevalence is increasing worldwide, leading to cardiometabolic morbidities. Adipocyte dysfunction, impairing white adipose tissue (WAT) expandability and metabolic flexibility, is central in the development of obesity-related metabolic complications. Rare syndromes of lipodystrophy characterized by an extreme paucity of functional adipose tissue should be considered as primary adipocyte dysfunction diseases. Berardinelli-Seip congenital lipodystrophy (BSCL) is the most severe form with a near absence of WAT associated with cardiometabolic complications such as insulin resistance, liver steatosis, dyslipidemia, and cardiomyopathy. Twenty years ago, mutations in the BSCL2 gene have been identified as the cause of BSCL in human. BSCL2 encodes seipin, an endoplasmic reticulum (ER) anchored protein whose function was unknown back then. Studies of seipin knockout mice or rats demonstrated how seipin deficiency leads to severe lipodystrophy and to cardiometabolic complications. At the cellular levels, seipin is organized in multimers that are particularly enriched at ER/lipid droplet and ER/mitochondria contact sites. Seipin deficiency impairs both adipocyte differentiation and mature adipocyte maintenance. Experiments using adipose tissue transplantation in seipin knockout mice and tissue-specific deletion of seipin have provided a large body of evidence that liver steatosis, cardiomyopathy, and renal injury, classical diabetic complications, are all consequences of lipodystrophy. Rare adipocyte dysfunctions such as in BSCL are the key paradigm to unravel the pathways that control adipocyte homeostasis. The knowledge gathered through the study of these pathologies may bring new strategies to maintain and improve adipose tissue expandability.

Keywords: adipocyte; adipocyte dysfunction; diabetic complications; insulin resistance; lipodystrophy; lipotoxicity; seipin.

Publication types

  • Review

MeSH terms

  • Adipocytes / metabolism*
  • Adipogenesis
  • Adipose Tissue / metabolism
  • Animals
  • Diabetes Complications
  • Disease Models, Animal
  • GTP-Binding Protein gamma Subunits / deficiency*
  • Genetic Association Studies* / methods
  • Genetic Predisposition to Disease*
  • Humans
  • Insulin Resistance
  • Lipid Metabolism
  • Lipodystrophy / diagnosis
  • Lipodystrophy / etiology
  • Lipodystrophy / metabolism
  • Lipolysis
  • Phenotype*
  • Rodentia
  • Severity of Illness Index


  • BSCL2 protein, human
  • Bscl2 protein, mouse
  • GTP-Binding Protein gamma Subunits