Ectodysplasin A Is Increased in Non-Alcoholic Fatty Liver Disease, But Is Not Associated With Type 2 Diabetes.

Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101555782 Publication Model: eCollection Cited Medium: Print ISSN: 1664-2392 (Print) Linking ISSN: 16642392 NLM ISO Abbreviation: Front Endocrinol (Lausanne) Subsets: MEDLINE

Original Publication: [Lausanne : Frontiers Research Foundation]

Insulin Resistance*; Cytokines/*metabolism ; Diabetes Mellitus, Type 2/*complications ; Diabetes Mellitus, Type 2/*metabolism ; Ectodysplasins/*blood ; Ectodysplasins/*metabolism ; Non-alcoholic Fatty Liver Disease/*complications ; Non-alcoholic Fatty Liver Disease/*metabolism; Adult ; Biomarkers/metabolism ; Biopsy ; Body Mass Index ; Cross-Sectional Studies ; Diabetes Mellitus, Type 2/blood ; Female ; Humans ; Inflammation ; Liver/metabolism ; Male ; Middle Aged ; Non-alcoholic Fatty Liver Disease/blood ; Obesity/blood ; Obesity/complications ; Obesity/metabolism ; RNA, Messenger/metabolism ; ROC Curve ; Sensitivity and Specificity

Ectodysplasin A (EDA) was recently identified as a liver-secreted protein that is increased in the liver and plasma of obese mice and causes skeletal muscle insulin resistance. We assessed if liver and plasma EDA is associated with worsening non-alcoholic fatty liver disease (NAFLD) in obese patients and evaluated plasma EDA as a biomarker for NAFLD. Using a cross-sectional study in a public hospital, patients with a body mass index >30 kg/m ² (n=152) underwent liver biopsy for histopathology assessment and fasting liver EDA mRNA. Fasting plasma EDA levels were also assessed. Non-alcoholic fatty liver (NAFL) was defined as >5% hepatic steatosis and nonalcoholic steatohepatitis (NASH) as NAFLD activity score ≥3. Patients were divided into three groups: No NAFLD (n=45); NAFL (n=65); and NASH (n=42). Liver EDA mRNA was increased in patients with NASH compared with No NAFLD (P=0.05), but not NAFL. Plasma EDA levels were increased in NAFL and NASH compared with No NAFLD (P=0.03). Plasma EDA was related to worsening steatosis (P=0.02) and fibrosis (P=0.04), but not inflammation or hepatocellular ballooning. ROC analysis indicates that plasma EDA is not a reliable biomarker for NAFL or NASH. Plasma EDA was not increased in patients with type 2 diabetes and did not correlate with insulin resistance. Together, we show that plasma EDA is increased in NAFL and NASH, is related to worsening steatosis and fibrosis but is not a reliable biomarker for NASH. Circulating EDA is not associated with insulin resistance in human obesity.
Clinical Trial Registration: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12615000875505, identifier ACTRN12615000875505.
Competing Interests: MW has received consultancy fees from Gilead Science, Inc. WB has received grants from Johnson and Johnson, Medtronic, GORE, Applied Medical, and Novo Nordisk, and personal fees from GORE, Novo Nordisk, and Merck Sharpe and Dohme for lectures and advisory boards. All were outside the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2021 Bayliss, Ooi, De Nardo, Shah, Montgomery, McLean, Kemp, Roberts, Brown, Burton and Watt.)

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Keywords: ectodysplasin A; hepatokine; insulin resistance; non-alcoholic fatty liver disease; type 2 diabetes (T2DM)

0 (Biomarkers)
0 (Cytokines)
0 (Ectodysplasins)
0 (RNA, Messenger)

Date Created: 20210322 Date Completed: 20220114 Latest Revision: 20220114

20221213

PMC7970300

10.3389/fendo.2021.642432

33746906