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

Authors: LI, YI-JIE - University Of Southern California; BAUMERT, BRITTNEY - University Of Southern California; STRATAKIS, NIKOS - Barcelona Institute For Global Health, Isglobal; GOODRICH, JESSE - University Of Southern California; WU, HAO-TIAN - Columbia University; HE, JING-XUAN - University Of Southern California; ZHAO, YIN-QI - University Of Southern California; AUNG, MAX - University Of Southern California; WANG, HONG-XU - University Of Southern California; ECKEL, SANDRAH - University Of Southern California; WALKER, DOUGLAS - Emory University; VALVI, DAMASKINI - The Icahn School Of Medicine At Mount Sinai; LA MERRILL, MICHELE - University Of California, Davis; RYDER, JUSTIN - Northwestern University; INGE, THOMAS - Northwestern University; JENKINS, TODD - University Of Cincinnati College Of Medicine; SISLEY, STEPHANIE - Children'S Nutrition Research Center (CNRC); KOHLI, ROHIT - Children'S Hospital Los Angeles; XANTHAKOS, STAVRA - University Of Cincinnati College Of Medicine; BACCARELLI, ANDREA - Columbia University; MCCONNELL, ROB - University Of Southern California; CONTI, DAVID - University Of Southern California; CHATZI, LIDA - University Of Southern California

Submitted to: World Journal of Gastroenterology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/9/2024
Publication Date: 1/9/2024
Citation: Li, Y., Baumert, B.O., Stratakis, N., Goodrich, J.A., Wu, H., He, J., Zhao, Y., Aung, M.T., Wang, H., Eckel, S.P., Walker, D.I., Valvi, D., La Merrill, M.A., Ryder, J.R., Inge, T.H., Jenkins, T., Sisley, S., Kohli, R., Xanthakos, S., Baccarelli, A.A., McConnell, R., Conti, D.V., Chatzi, L. 2024. Circulating microRNA expression and nonalcoholic fatty liver disease in adolescents with severe obesity. World Journal of Gastroenterology. 30(4):332-345. https://doi.org/10.3748/wjg.v30.i4.332.
DOI: https://doi.org/10.3748/wjg.v30.i4.332

Interpretive Summary: Scientists didn't know how tiny molecules called microRNAs in our blood relate to a liver problem called non-alcoholic fatty liver disease (NAFLD) in teenagers. NAFLD is a common liver disease in kids and teens with obesity. Researchers in Houston, Texas studied teenagers with severe obesity, 81 with NAFLD and 54 without it. They found that some microRNAs were expressed differently in teens with NAFLD. They also found that these microRNAs were linked to pathways like cancer and hepatitis (liver damaging viruses). This study helps understand how NAFLD may occur and might lead to new ways to diagnose and treat earlier, which could help keep kids and teens with obesity become healthier.

Technical Abstract: 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.