Ji Yang1, Wenjing Zhou1, Jinzhou Zhu2, Yue Wu1, Liqian Xu1, Yuming Wang1, Qin Zhang1, Yunmei Yang3. 1. Department of Geriatrics, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China. 2. Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu, China. 3. Department of Geriatrics, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China. Electronic address: 1194070@zju.edu.cn.
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.
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.
Authors: Jacqueline Bayliss; Geraldine J Ooi; William De Nardo; Yazmin Johari Halim Shah; Magdalene K Montgomery; Catriona McLean; William Kemp; Stuart K Roberts; Wendy A Brown; Paul R Burton; Matthew J Watt Journal: Front Endocrinol (Lausanne) Date: 2021-03-04 Impact factor: 5.555
Authors: Dawn K Coletta; Leslea J Hlusko; G Richard Scott; Luis A Garcia; Celine M Vachon; Aaron D Norman; Janet L Funk; Gabriel Q Shaibi; Valentina Hernandez; Eleanna De Filippis; Lawrence J Mandarino Journal: PLoS One Date: 2021-10-07 Impact factor: 3.240