Tobaruela-Resola Ana Luz, Milagro Fermín I, Elorz Mariana, Benito-Boillos Alberto, Herrero José I, Mogna-Peláez Paola, Tur Josep A, Martínez J Alfredo, Abete Itziar, Zulet M Ángeles
Department of Nutrition, Food Sciences and Physiology and Centre for Nutrition Research, Faculty of Pharmacy and Nutrition, University of Navarra, 31008, Pamplona, Spain.
Navarra Institute for Health Research (IdiSNA), 31008, Pamplona, Spain.
J Physiol Biochem. 2024 Aug 14. doi: 10.1007/s13105-024-01037-8.
Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is a worldwide leading cause of liver-related associated morbidities and mortality. Currently, there is a lack of reliable non-invasive biomarkers for an accurate of MASLD. Hence, this study aimed to evidence the functional role of miRNAs as potential biomarkers for MASLD assessment. Data from 55 participants with steatosis (MASLD group) and 45 without steatosis (control group) from the Fatty Liver in Obesity (FLiO) Study (NCT03183193) were analyzed. Anthropometrics and body composition, biochemical and inflammatory markers, lifestyle factors and liver status were evaluated. Circulating miRNA levels were measured by RT-PCR. Circulating levels of miR-122-5p, miR-151a-3p, miR-126-5p and miR-21-5p were significantly increased in the MASLD group. These miRNAs were significantly associated with steatosis, liver stiffness and hepatic fat content. Logistic regression analyses revealed that miR-151a-3p or miR-21-5p in combination with leptin showed a significant diagnostic accuracy for liver stiffness obtaining an area under the curve (AUC) of 0.76 as well as miR-151a-3p in combination with glucose for hepatic fat content an AUC of 0.81. The best predictor value for steatosis was obtained by combining miR-126-5p with leptin, presenting an AUC of 0.95. Circulating miRNAs could be used as a non-invasive biomarkers for evaluating steatosis, liver stiffness and hepatic fat content, which are crucial in determining MASLD. CLINICAL TRIAL REGISTRATION: • Trial registration number: NCT03183193 ( www.clinicaltrials.gov ). • Date of registration: 12/06/2017.
代谢功能障碍相关脂肪性肝病（MASLD）是全球范围内导致肝脏相关发病率和死亡率的主要原因。目前，缺乏用于准确诊断MASLD的可靠非侵入性生物标志物。因此，本研究旨在证明微小RNA（miRNA）作为MASLD评估潜在生物标志物的功能作用。分析了来自肥胖脂肪肝（FLiO）研究（NCT03183193）的55名有脂肪变性的参与者（MASLD组）和45名无脂肪变性的参与者（对照组）的数据。评估了人体测量学和身体成分、生化和炎症标志物、生活方式因素及肝脏状况。通过逆转录聚合酶链反应（RT-PCR）测量循环miRNA水平。MASLD组中miR-122-5p、miR-151a-3p、miR-126-5p和miR-21-5p的循环水平显著升高。这些miRNA与脂肪变性、肝脏硬度和肝脂肪含量显著相关。逻辑回归分析显示，miR-151a-3p或miR-21-5p与瘦素联合使用时，对肝脏硬度具有显著的诊断准确性，曲线下面积（AUC）为0.76；miR-151a-3p与葡萄糖联合使用时，对肝脂肪含量的AUC为0.81。miR-126-5p与瘦素联合使用时，对脂肪变性的预测价值最佳，AUC为0.95。循环miRNA可作为评估脂肪变性、肝脏硬度和肝脂肪含量的非侵入性生物标志物，这些指标在确定MASLD中至关重要。临床试验注册：•试验注册号：NCT03183193（www.clinicaltrials.gov）。•注册日期：2017年6月12日。
