Circulating microRNAs are associated with metabolic markers in adolescents with hepatosteatosis

Authors: LIN, HAIXIA - Arkansas Children'S Nutrition Research Center (ACNC); MERCER, KELLY - Arkansas Children'S Nutrition Research Center (ACNC); OU, XIAWEI - Arkansas Children'S Nutrition Research Center (ACNC); MANSFIELD, KORI - University Arkansas For Medical Sciences (UAMS); BUCHMANN, ROBERT - University Arkansas For Medical Sciences (UAMS); BORSHEIM, ELISABET - Arkansas Children'S Nutrition Research Center (ACNC); TAS, EMIR - Arkansas Children'S Nutrition Research Center (ACNC)

Submitted to: Frontiers in Endocrinology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/14/2022
Publication Date: 4/14/2022
Citation: Lin, H., Mercer, K., Ou, X., Mansfield, K., Buchmann, R., Borsheim, E., Tas, E. 2022. Circulating microRNAs are associated with metabolic markers in adolescents with hepatosteatosis. Frontiers in Endocrinology. https://doi.org/10.3389/fendo.2022.856973.
DOI: https://doi.org/10.3389/fendo.2022.856973

Interpretive Summary: Investigators at Arkansas Children’s Nutrition Center was seeking to enhance knowledge about whether regulation of gene expression is impacted in children with obesity that also have insulin resistance and/or elevated liver fat compared to children with “healthy obesity” Therefore, they studied the circulating microRNAs, glucose, and insulin concentrations, as well as liver fat content (using magnetic resonance imaging) in adolescent children with obesity. The microRNAs are small molecules that regulate the type and amount of proteins a cell is making. Adolescents with obesity were stratified based on insulin resistance and liver fat status. Differentially expressed miRNAs were compared between groups and correlated with metabolic markers and liver fat. The investigators found that several miRNAs were differentially expressed in children with insulin resistance and elevated liver fat content. Measurements of circulating microRNAs may be a useful tool in studies aiming to prevent insulin resistance and fatty liver in children and adolescents with obesity.

Technical Abstract: Background: Altered hepatic microRNA (miRNA) expression may play a role in the development of insulin resistance (IR) and non-alcoholic fatty liver disease (NAFLD). Circulating miRNAs could mirror the liver metabolism. Objective: This study aimed to assess the relationship between serum miRNA profile in children with obesity, IR, and NAFLD. Methods: Adolescents with obesity (n = 31) were stratified based on insulin resistance and NAFLD status. One-hundred seventy-nine miRNAs were determined in the serum by quantitative RT-PCR. Differentially expressed miRNAs were compared between groups, and log-transformed levels correlated with metabolic markers and intrahepatic triglyceride. Results: Serum miR-21-5p, -22-3p, -150-5p, and -155-5p levels were higher in children with IR and NAFLD, and their expression levels correlated with hepatic fat and serum triglyceride. In patients with NAFLD, miR-155-5p correlated with ALT (r = 0.68, p<0.01) and AST (r = 0.64, p<0.01) and miR-21-5p and -22-3p levels correlated with plasma adiponectin (r = -0.71 and r = -0.75, respectively, p<0.05) and fibroblast growth factor-21 (r = -0.73 and r = -0.89, respectively, p<0.01). miR-27-3a level was higher in children without IR and NAFLD. Conclusions: Several miRNAs are differentially expressed in children with IR and NAFLD. Determining their mechanistic roles may provide newer diagnostic tools and therapeutic targets for pediatric NAFLD. Key words / Mesh terms: childhood obesity, insulin resistance, liver disease, MRI, microRNA