Abstract
Acquired generalized lipodystrophy (AGL) is a rare condition characterized by an altered distribution of adipose tissue and predisposition to develop hepatic steatosis and fibrosis, diabetes, and hypertriglyceridemia. Diagnosis of AGL is based on the observation of generalized fat loss, autoimmunity and lack of family history of lipodystrophy. The pathogenic mechanism of fat destruction remains unknown but evidences suggest an autoimmune origin. Anti-adipocyte antibodies have been previously reported in patients with AGL, although their involvement in the pathogenesis has been poorly studied and the autoantibody target/s remain/s to be identified. Using a combination of immunochemical and cellular studies, we investigated the presence of anti-adipocyte autoantibodies in patients with AGL, acquired partial lipodystrophy, localized lipoatrophy due to intradermic insulin injections or systemic lupus erythematosus. Moreover, the impact of anti-adipocyte autoantibodies from AGL patients was assessed in cultured mouse preadipocytes. Following this approach, we identified anti-perilipin 1 IgG autoantibodies in the serum of patients with autoimmune variety-AGL, but in no other lipodystrophies tested. These autoantibodies altered the ability of perilipin 1 to regulate lipolysis in cultured preadipocytes causing abnormal, significantly elevated basal lipolysis. Our data provide strong support for the conclusion that perilipin 1 autoantibodies are a cause of generalized lipodystrophy in these patients.
Highlights
Acquired generalized lipodystrophy (AGL), or Lawrence syndrome (ORPHA:79086), is a rare disease that usually develops during childhood and adolescence
We used the criteria for designating AGL variety described by Misra and Garg [3]: I) Autoimmune variety: AGL follows an autoimmune diseases or the presence of autoantibodies; II) Panniculitis variety: Tender subcutaneous nodules that herald the Abbreviations: AGL, acquired generalized lipodystrophy; APL, acquired partial lipodystrophy; ATGL, adipose triacylglycerol lipase; CGI-58, comparative gene identification-58; FPLD4, familial partial lipodystrophy type 4; hMSCs, human mesenchymal stem cells; HSL, hormone-sensitive lipase; IBMX, isobutylmethylxanthine; I-LA, localized lipoatrophy due to intradermic insulin injections; PLIN, perilipin; SLE, systemic lupus erythematous
This study provides the first evidence for the presence of autoantibodies against the lipid droplet protein perilipin 1 (PLIN1) in patients with AGL
Summary
Acquired generalized lipodystrophy (AGL), or Lawrence syndrome (ORPHA:79086), is a rare disease that usually develops during childhood and adolescence. It is characterized by a selective loss of adipose tissue from large areas of the body, the face, arms, and legs [1]. 25% of patients debut with an episode of panniculitis. Another 25% of cases present associated autoimmune diseases, juvenile dermatomyositis. The metabolic complications are typically less severe in patients with the panniculitis-associated phenotype compared with the other two subtypes [3]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
