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 patientsFC, ML-T, AL-L, and SG were supported by grants PI15-
00255 from Instituto de Salud Carlos III (ISCIII, Ministerio de
Economía y Competitividad) and Fondos FEDER, Complemento
II-CM network (B2017/BMD3673), Acciones Cooperativas y
Complementarias Intramurales (ACCI) from CIBERER (ISCIII),
and Fundación SENEFRO. MdMwas supported by Roche Farma
SA and Foundation Domingo Martínez. VA was financed by
Consejería de Educación, Juventud y Deporte of Comunidad
de Madrid and by Fondo Social Europeo (Programa Operativo
de Empleo Juvenil, and Iniciativa de Empleo Juvenil (YEI),
(PEJ15/BIO/AI/0045). DA-V was supported by the intramural
research program of the Xunta de Galicia (Programa de
Consolidación e Estructuración de Unidades de Investigación
Competitivas, grant ED341b 2017/19), by the Instituto de Salud
Carlos III (grant number: PI08-1449) and the European Regional
Development Fund, FEDER and by the Asociación Española de
Familiares y Afectados de Lipodistrofias (AELIP
