DOI: 10.36347/sjmcr.2022.v10i04.016

Pages: 329-333

Life without adipose tissue: Congenital generalized lipodystrophy; Origin, pathophysiology and therapeutic management Congenital Generalized Lipodystrophies also known as Berardinelli-Seip Congenital Lipodystrophy (BSCL) represent the most extreme phenotype of lipodystrophies. BSCLs are characterized by an almost total loss of adipose tissue and a predisposition to develop metabolic complications such as diabetes, hypertriglyceridemia ( hyperTG) and non-alcoholic fatty liver disease (NAFLD). Four subtypes of BSCL are distinguished according to the gene involved: AGPAT2 encoding the enzyme 1-acylglycerol-3-phosphate O acyltransferase 2, BSCL2 encoding Seipin, and more rarely CAV1 and PTRF encoding caveolae-associated proteins, respectively Caveolin-1, and Polymerase 1 and Transcription Releasing Factor (also known as Cavin-1). The study of the pathophysiology of BSCL, through clinical work and the generation of relevant animal and cellular models, has made it possible to understand how the absence of these proteins leads to primary and severe adipocyte dysfunction. It also highlights the critical importance of the adipose tissue in carbohydrate-lipid homeostasis, through its role as a storage site for energy molecules and its endocrine action. In this article, we will focus on the clinical features, molecular mechanisms, and treatment of congenital lipodystrophies. BSCL is an extreme phenotype that provides a unique opportunity to study the pathophysiological consequences of life without adipose tissue.