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©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 28, 2024; 30(4): 332-345
Published online Jan 28, 2024. doi: 10.3748/wjg.v30.i4.332
Circulating microRNA expression and nonalcoholic fatty liver disease in adolescents with severe obesity
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
Yi-Jie Li, Brittney O Baumert, Jesse A Goodrich, Jing-Xuan He, Yin-Qi Zhao, Max T Aung, Hong-Xu Wang, Sandrah P Eckel, Rob McConnell, David V Conti, Lida Chatzi, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA 90032, United States
Nikos Stratakis, Barcelona Institute of Global Health, Barcelona Institute of Global Health, Barcelona 08036, Spain
Hao-Tian Wu, Andrea A Baccarelli, Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY 10032, United States
Douglas I Walker, Gangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA 30329, United States
Damaskini Valvi, Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States
Michele A La Merrill, Department of Environmental Toxicology, University of California, Davis, CA 95616, United States
Justin R Ryder, Thomas H Inge, Department of Surgery, Lurie Children’s Hospital of Chicago, Chicago, IL 60611, United States
Justin R Ryder, Thomas H Inge, Northwestern University Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, United States
Todd Jenkins, Division of Biostatistics and Epidemiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, United States
Todd Jenkins, Stavra A Xanthakos, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, United States
Stephanie Sisley, Department of Pediatrics, Children’s Nutrition Research Center USDA/ARS, Baylor College of Medicine, Houston, TX 77030, United States
Rohit Kohli, Department of Gastroenterology, Children’s Hospital Los Angeles, Los Angeles, CA 90027, United States
Stavra A Xanthakos, Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, United States
Author contributions: Li YJ and Chatzi L designed the research study; Li YJ performed the research; Conti DV, Stratakis N, Goodrich JA, Zhao YQ, Wang HX, and He JX contributed new analytic tools; Ryder JR, Inge TH, Jenkins T, Sisley S, Kohli R and Xanthakos SA contributed data collection; Li YJ wrote the manuscript; Baumert BO, Stratakis N, Goodrich JA, Wu HT, Aung MT, Eckel SP, Walker DI, Valvi D, La Merrill MA, Ryder JR, Inge TH, Jenkins T, Sisley S, Kohli R, Xanthakos SA, Baccarelli AA, McConnell R, Conti DV and Chatzi L reviewed and revised manuscript; all authors have read and approve the final manuscript.
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; and The Teen-LABS Consortium: National Institute of Diabetes and Digestive and Kidney Diseases, No. UM1DK072493 and No. UM1DK095710.
Institutional review board statement: This study used data from the Teen-LABS study (ClinicalTrials.gov NCT00465829), under a protocol approved by the institutional review boards of the participating institutions: Cincinnati Children’s Hospital Medical Center (Cincinnati, Ohio), Nationwide Children’s Hospital (Columbus, Ohio), University of Pittsburgh Medical Center (Pittsburgh, Pennsylvania), Texas Children’s Hospital (Houston, Texas), and Children’s Hospital of Alabama (Birmingham, Alabama).
Informed consent statement: This is a secondary data analysis, which means we do not have informed consent nor any private information of participants.
Conflict-of-interest statement: There are no conflicts of interest to report.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at
chatzi@usc.edu.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Lida Chatzi, MD, PhD, Professor, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, 1845 N. Soto Street, Los Angeles, CA 90032, United States.
chatzi@usc.edu
Received: September 29, 2023
Peer-review started: September 29, 2023
First decision: November 6, 2023
Revised: December 4, 2023
Accepted: January 9, 2024
Article in press: January 9, 2024
Published online: January 28, 2024
Processing time: 118 Days and 23.4 Hours
ARTICLE HIGHLIGHTS
Research background
Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver diseases in the world, impacting approximately 25% of the population. The gold standard for NAFLD diagnosis is liver biopsy, yet it is invasive and expensive. Therefore, it is essential to provide alternative methods for NAFLD diagnosis. Recent studies propose that plasma microRNAs (miRNAs) are potential biomarkers for NAFLD, though research in this area remains limited.
Research motivation
This study is motivated by the current gaps of concerning associations between plasma miRNAs and NAFLD. This study aims to identify potential biomarkers for NAFLD diagnosis and NAFLD progression.
Research objectives
The objective of this study is to investigate associations between histological features of NAFLD and plasma miRNAs in adolescents with severe obesity.
Research methods
A total of 135 participants from the Teen Longitudinal Assessment of Bariatric Surgery (Teen-LABS) study were included in this study. Within Teen-LABS, the histological features of NAFLD, including NAFLD, nonalcoholic steatohepatitis (NASH), ballooning degeneration, fibrosis, and lobular inflammation, are characterized based on liver biopsy. Multivariate logistic regression was employed to investigates associations between NAFLD features and 843 plasma miRNAs. Pathway analysis was performed for identified NAFLD-associated miRNA by Ingenuity Pathway Analysis (IPA).
Research results
In the present study, we identified 38, 52, 16, 15, and 9 plasma miRNAs associated with NAFLD, NASH, fibrosis, ballooning, and lobular inflammation, respectively. Among these miRNA, miR-122-5p, miR-1343-5p, miR-193a-5p, miR-193b-5p, and miR-7845-5p were consistently upregulated across NAFLD features. In contrast, miR-1296-5p, miR-1301-5p, miR-199b-5p, miR-411-5p, and miR-6885-3p were positively associated with NAFLD, yet displayed predominant decreasing in NASH, fibrosis, ballooning, and lobular inflammation. IPA results suggested that most of NAFLD-associated miRNAs were related to cancer.
Research conclusions
Positive and consistent associations were observed between miR-122-5p, miR-1343-5p, miR-193a-5p, miR-193b-5p, and miR-7845-5p and NAFLD features, indicating their potential as biomarkers for NAFLD diagnosis. Additionally, miR-1296-5p, miR-1301-5p, miR-199b-5p, miR-411-5p, and miR-6885-3p showed different patterns of expression in response to NAFLD severity, indicating they had potential for characterizing NAFLD progression.
Research perspectives
Conducting studies with larger and more diverse populations would contribute to more conclusive findings regarding NAFLD–miRNA associations. Furthermore, experimental research is imperative to understand the underlying molecular mechanisms of NAFLD-miRNA associations.
