Circulating ectodysplasin A is a potential biomarker for nonalcoholic fatty liver disease

Abstract Background Ectodysplasin A (EDA), a new hepatokine, may be involved in energy metabolism. This study aims to 1) investigate the role of EDA in hepatic steatosis in C57BL/6 mice and HepG2 cells; 2) evaluate serum EDA in nonalcoholic fatty liver disease (NAFLD) in human. Methods This study comprises an experimental study in vitro and in vivo and a hospital based case-control study. Western blotting, qPCR and ELISA were used to measure EDA levels. siRNA and shRNA were performed to knockdown EDA. An Adipokine Magnetic Bead Panel was performed to measure serum adipokines. Results Increased levels of hepatic and secreted EDA were detected in steatosis, in vivo and in vitro. Steatosis was ameliorated by EDA knockdown in vitro, while intrahepatic triglycerides content and liver enzymes were improved in vivo. Furthermore, knockdown of EDA upregulated lipolytic genes and suppressed lipogenic genes. Serum EDA in subjects with NAFLD was higher. Moreover, it reveals associations between circulating EDA and higher odds of NAFLD, while circulating EDA presented a practicable performance to identify NAFLD. Lastly, serum EDA level was dependent on BMI, TNF-α, T2DM and obesity. Conclusions EDA aggravates steatosis by striking balance between lipid deposition and elimination. It was a potential biomarker of NAFLD.