外胚层发育不良相关蛋白 A 在非酒精性脂肪性肝病中增加，但与 2 型糖尿病无关。

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

机构信息

Department of Anatomy and Physiology, The University of Melbourne, Melbourne, VIC, Australia.

Department of Surgery, Centre for Obesity Research and Education, Monash University, Melbourne, VIC, Australia.

出版信息

Front Endocrinol (Lausanne). 2021 Mar 4;12:642432. doi: 10.3389/fendo.2021.642432. eCollection 2021.

DOI:10.3389/fendo.2021.642432

PMID:33746906

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7970300/

Abstract

UNLABELLED

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 (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 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.

摘要

目的

评估肥胖患者肝及血浆外显子 15 缺失蛋白 A（EDA）与非酒精性脂肪性肝病（NAFLD）恶化的相关性，并探讨其是否可作为 NAFLD 的生物标志物。

方法

本研究采用横断面研究方法，纳入在公立医院就诊的 BMI＞30kg/m2 的患者，进行肝组织活检和肝 EDA mRNA 检测，并检测空腹血浆 EDA 水平。根据肝组织学诊断将患者分为非脂肪性肝病（NAFL）组（n=45）、单纯性脂肪性肝病（NAFL）组（n=65）和非酒精性脂肪性肝炎（NASH）组（n=42）。

结果

与非脂肪性肝病组相比，NASH 组患者肝 EDA mRNA 表达升高（P=0.05），但与单纯性脂肪性肝病组患者相比差异无统计学意义。NAFL 和 NASH 组患者的血浆 EDA 水平均高于非脂肪性肝病组（P=0.03）。ROC 分析显示，血浆 EDA 水平不能可靠地预测 NAFL 或 NASH。2 型糖尿病患者的血浆 EDA 水平并未升高，且与胰岛素抵抗无关。