Estudo da relação entre PARP-1 e adiponectina em pessoas com lipodistrofia generalizada congênita tipo 2

Abstract

Adipogenesis is strongly influenced by poly(ADP-ribose) polymerase-1 (PARP-1), which regulates transcription factors such as PPARγ and C/EBPβ. PARP-1 mediates obesity and adipocyte hypertrophy, and its alteration causes hepatic fat accumulation and dyslipidemia in mice, features also present in Congenital Generalized Lipodystrophy (CGL), a set of rare diseases characterized by subcutaneous adipose tissue (sWAT) deficiency. Affected individuals have low levels of adiponectin (APN), which has important metabolic properties. In murine cardiac fibroblasts, PARP-1 is a transcriptional repressor of APN through poly(ADP-ribosylation) of PPARγ. That said, we observed PARP-1 expression in people with CGL types 1 and 2 and, in individuals with CGL2 (CGL type 2), we analyzed its relationship with APN levels. We collected peripheral blood samples from 4 individuals with CGL1 (CGL type 1), 16 with CGL2 and 29 controls, separated the plasma, extracted and quantified leukocyte DNA in order to confirm the diagnosis of CGL2 through capillary DNA sequencing, and analyzed PARP-1 mRNA levels by qPCR. Western blotting for APN was done using plasma. We found that PARP-1 expression was significantly lower in CGL2 patients compared to controls (p<0.05). Furthermore, such expression is negatively correlated with APN levels (p=0.034), indicating that PARP-1 may be an APN regulator in CGL2. More studies are needed on the role of this relationship in the context of a generalized congenital sWAT loss.