Abstract
Obesity-related glomerulopathy is a secondary glomerular disease and its incidence has been increased globally in parallel with the obesity epidemic. ORG emerged as a growing cause of end-stage renal disease in recent years. Unbalanced production of adipokines at the adipose tissue as well as low-grade inflammatory processes play central roles in ORG progression. ORG mouse model with ACE2-knockout was generated and kidney injury was evaluated by biochemistry and histological staining assays. Protein and mRNA expressions were quantified by ELISA, western blot or qRT-PCR methods. ACE2 deficiency aggravated ORG-related renal injuries and stimulated both lipid accumulation and inflammatory responses. Further, Nrf2 pathway was deactivated upon ACE2-knockout. By contrast, ACE2 overexpression reactivated Nrf2 pathway and ameliorated ORG symptoms by decreasing fat deposition and reducing inflammatory responses. Our data demonstrated that ACE2 exerted the beneficial effects by acting through Nrf2 signaling pathway, suggesting the protective role of ACE2 against lipid accumulation and inflammatory responses in ORG pathogenesis.