Circulating microRNA expression and nonalcoholic fatty liver disease in adolescents with severe obesity  

作　　者：Yi-Jie Li Brittney O Baumert Nikos Stratakis Jesse A Goodrich Hao-Tian Wu Jing-Xuan He Yin-Qi Zhao Max T Aung Hong-Xu Wang Sandrah P Eckel Douglas I Walker Damaskini Valvi Michele A La Merrill Justin R Ryder Thomas H Inge Todd Jenkins Stephanie Sisley Rohit Kohli Stavra A Xanthakos Andrea A Baccarelli Rob McConnell David V Conti Lida Chatzi 

机构地区：[1]Department of Population and Public Health Sciences,Keck School of Medicine,University of Southern California,Los Angeles,CA 90032,United States [2]Barcelona Institute of Global Health,Barcelona Institute of Global Health,Barcelona 08036,Spain [3]Department of Environmental Health Sciences,Mailman School of Public Health,Columbia University,New York,NY 10032,United States [4]Gangarosa Department of Environmental Health,Rollins School of Public Health,Emory University,Atlanta,GA 30329,United States [5]Department of Environmental Medicine and Public Health,Icahn School of Medicine at Mount Sinai,New York,NY 10029,United States [6]Department of Environmental Toxicology,University of California,Davis,CA 95616,United States [7]Department of Surgery,Lurie Children’s Hospital of Chicago,Chicago,IL 60611,United States [8]Northwestern University Feinberg School of Medicine,Northwestern University,Chicago,IL 60611,United States [9]Division of Biostatistics and Epidemiology,Cincinnati Children's Hospital Medical Center,Cincinnati,OH 45229,United States [10]Department of Pediatrics,University of Cincinnati College of Medicine,Cincinnati,OH 45229,United States [11]Department of Pediatrics,Children’s Nutrition Research Center USDA/ARS,Baylor College of Medicine,Houston,TX 77030,United States [12]Department of Gastroenterology,Children’s Hospital Los Angeles,Los Angeles,CA 90027,United States [13]Division of Gastroenterology,Hepatology and Nutrition,Cincinnati Children's Hospital Medical Center,Cincinnati,OH 45229,United States

出　　处：《World Journal of Gastroenterology》2024年第4期332-345,共14页世界胃肠病学杂志（英文版）

基　　金：Supported by National Institute of Environmental Health,No.R01ES030691;No.R01ES030364,No.R01ES029944,No.U01HG013288,No.T32-ES013678,No.P30ES007048,No.U2CES030859,No.R01ES032831,No.R01ES033688,No.P30ES023515,and No.P2CES033433;National Human Genome Research Institute and National Institute of Environmental Health,No.U01HG013288;California Environmental Protection Agency,No.20-E0017;National Cancer Institute and National Institute of Environmental Health,No.P01CA196569;Ministry of Science and Innovation and State Research Agency,No.CEX2018-000806-S;European Union(“NextGenerationEU/PRTR”),No.IJC2020-043630-I;European Union’s Horizon Europe Research And Innovation Programme Under the Marie Skłodowska-Curie Actions Postdoctoral Fellowships,No.101059245;United States Department of Agriculture,No.6250-51000-053;National Institutes of Health,No.R01DK128117-01A1;The Teen-LABS Consortium:National Institute of Diabetes and Digestive and Kidney Diseases,No.UM1DK072493 and No.UM1DK095710.

摘　　要：BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is one of the most common chronic liver diseases in children and adolescents.NAFLD ranges in severity from isolated hepatic steatosis to nonalcoholic steatohepatitis(NASH),wherein hepatocellular inflammation and/or fibrosis coexist with steatosis.Circulating microRNA(miRNA)levels have been suggested to be altered in NAFLD,but the extent to which miRNA are related to NAFLD features remains unknown.This analysis tested the hypothesis that plasma miRNAs are significantly associated with histological features of NAFLD in adolescents.AIM To investigate the relationship between plasma miRNA expression and NAFLD features among adolescents with NAFLD.METHODS This study included 81 adolescents diagnosed with NAFLD and 54 adolescents without NAFLD from the Teen-Longitudinal Assessment of Bariatric Surgery study.Intra-operative core liver biopsies were collected from participants and used to characterize histological features of NAFLD.Plasma samples were collected during surgery for miRNA profiling.A total of 843 plasma miRNAs were profiled using the HTG EdgeSeq platform.We examined associations of plasma miRNAs and NAFLD features using logistic regression after adjusting for age,sex,race,and other key covariates.Ingenuity Pathways Analysis was used to identify biological functions of miRNAs that were associated with multiple histological features of NAFLD.RESULTS We identified 16 upregulated plasma miRNAs,including miR-193a-5p and miR-193b-5p,and 22 downregulated plasma miRNAs,including miR-1282 and miR-6734-5p,in adolescents with NAFLD.Moreover,52,16,15,and 9 plasma miRNAs were associated with NASH,fibrosis,ballooning degeneration,and lobular inflammation,respectively.Collectively,16 miRNAs were associated with two or more histological features of NAFLD.Among those miRNAs,miR-411-5p was downregulated in NASH,ballooning,and fibrosis,while miR-122-5p,miR-1343-5p,miR-193a-5p,miR-193b-5p,and miR-7845-5p were consistently and positively associated with all histological features

关 键 词：MicroRNA Nonalcoholic fatty liver disease Non-alcoholic steatohepatitis Liver fibrosis Lobular inflammation Ballooning degeneration 

分 类 号：R575.5[医药卫生—消化系统]