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

Ballooning degeneration Liver fibrosis Lobular inflammation MicroRNA Non-alcoholic steatohepatitis Nonalcoholic fatty liver disease

Journal

World journal of gastroenterology
ISSN: 2219-2840
Titre abrégé: World J Gastroenterol
Pays: United States
ID NLM: 100883448

Informations de publication

Date de publication:
28 Jan 2024
Historique:
received: 29 09 2023
revised: 04 12 2023
accepted: 09 01 2024
medline: 5 2 2024
pubmed: 5 2 2024
entrez: 5 2 2024
Statut: ppublish

Résumé

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. To investigate the relationship between plasma miRNA expression and NAFLD features among adolescents with NAFLD. 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. 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 of NAFLD. Pathway analysis revealed that most common pathways of miRNAs associated with multiple NAFLD features have been associated with tumor progression, while we also identified linkages between miR-122-5p and hepatitis C virus and between miR-199b-5p and chronic hepatitis B. Plasma miRNAs were associated with NAFLD features in adolescent with severe obesity. Larger studies with more heterogeneous NAFLD phenotypes are needed to evaluate miRNAs as potential biomarkers of NAFLD.

Sections du résumé

BACKGROUND 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 OBJECTIVE
To investigate the relationship between plasma miRNA expression and NAFLD features among adolescents with NAFLD.
METHODS 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 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 of NAFLD. Pathway analysis revealed that most common pathways of miRNAs associated with multiple NAFLD features have been associated with tumor progression, while we also identified linkages between miR-122-5p and hepatitis C virus and between miR-199b-5p and chronic hepatitis B.
CONCLUSION CONCLUSIONS
Plasma miRNAs were associated with NAFLD features in adolescent with severe obesity. Larger studies with more heterogeneous NAFLD phenotypes are needed to evaluate miRNAs as potential biomarkers of NAFLD.

Identifiants

DOI: 10.3748/wjg.v30.i4.332 PMID: 38313232 PMC: PMC10835537
pubmed: 38313232
doi: 10.3748/wjg.v30.i4.332
pmc: PMC10835537
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

332-345

Informations de copyright

©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.

Déclaration de conflit d'intérêts

Conflict-of-interest statement: There are no conflicts of interest to report.

Auteurs

Yi-Jie Li (YJ)

Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA 90032, United States.

Brittney O Baumert (BO)

Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA 90032, United States.

Nikos Stratakis (N)

Barcelona Institute of Global Health, Barcelona Institute of Global Health, Barcelona 08036, Spain.

Jesse A Goodrich (JA)

Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA 90032, United States.

Hao-Tian Wu (HT)

Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY 10032, United States.

Jing-Xuan He (JX)

Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA 90032, United States.

Yin-Qi Zhao (YQ)

Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA 90032, United States.

Max T Aung (MT)

Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA 90032, United States.

Hong-Xu Wang (HX)

Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA 90032, United States.

Sandrah P Eckel (SP)

Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA 90032, United States.

Douglas I Walker (DI)

Gangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA 30329, United States.

Damaskini Valvi (D)

Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States.

Michele A La Merrill (MA)

Department of Environmental Toxicology, University of California, Davis, CA 95616, United States.

Justin R Ryder (JR)

Department of Surgery, Lurie Children's Hospital of Chicago, Chicago, IL 60611, United States.
Northwestern University Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, United States.

Thomas H Inge (TH)

Department of Surgery, Lurie Children's Hospital of Chicago, Chicago, IL 60611, United States.
Northwestern University Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, United States.

Todd Jenkins (T)

Division of Biostatistics and Epidemiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, United States.
Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, United States.

Stephanie Sisley (S)

Department of Pediatrics, Children's Nutrition Research Center USDA/ARS, Baylor College of Medicine, Houston, TX 77030, United States.

Rohit Kohli (R)

Department of Gastroenterology, Children's Hospital Los Angeles, Los Angeles, CA 90027, United States.

Stavra A Xanthakos (SA)

Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, United States.
Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, United States.

Andrea A Baccarelli (AA)

Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY 10032, United States.

Rob McConnell (R)

Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA 90032, United States.

David V Conti (DV)

Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA 90032, United States.

Lida Chatzi (L)

Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA 90032, United States. chatzi@usc.edu.

Classifications MeSH