Circulating miRNA signatures associated with insulin resistance in adolescents with obesity

Authors: LIN, HAIXIA - ARKANSAS CHILDREN'S NUTRITION RESEARCH CENTER (ACNC); TAS, EMIR - UNIVERSITY ARKANSAS FOR MEDICAL SCIENCES (UAMS); BORSHEIM, ELISABET - UNIVERSITY ARKANSAS FOR MEDICAL SCIENCES (UAMS); MERCER, KELLY - ARKANSAS CHILDREN'S NUTRITION RESEARCH CENTER (ACNC)

Submitted to: Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/7/2020
Publication Date: 10/8/2020
Citation: Lin, H., Tas, E., Borsheim, E., Mercer, K.E. 2020. Circulating miRNA signatures associated with insulin resistance in adolescents with obesity. Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy. 13:4929–4939. https://doi.org/10.2147/DMSO.S273908.
DOI: https://doi.org/10.2147/DMSO.S273908

Interpretive Summary: Childhood obesity is linked to metabolic disorders, which increases the risk of developing insulin resistance (IR), nonalcoholic fatty liver disease, type II diabetes in adulthood. Mechanistic biomarkers may be beneficial for early identification of obesity-associated complications. MicroRNAs (miRNAs) as regulatory molecules are implicated in insulin signaling and metabolic pathways. Therefore, identifying circulating miRNA signatures will provide new insights into a better understanding of etiopathogenesis of obesity-related comorbidities. In the present study, we aimed to determine if there are unique circulating miRNA profiles that can indicate IR in a group of obese adolescents. Adolescents (aged 10-17 years) with obesity were recruited from a weight management clinic. Fasting serum samples were tested for miRNA profiles using a quantitative RT-PCR-based miRNA Focus Panel. Associations between identified miRNA expressions and IR and adiposity were examined. We found 12 elevated miRNAs linked to IR in obese adolescents. Of them, miR-30d, -221, and -122 distinguished adolescents with IR from those with obesity and also reflected the severity of obesity. It may highlight the potential implications of miRNA-based biomarkers for early identification IR in obese individuals different from conventional serum indicators. To our knowledge, this is the first report showing that circulating miRNAs can serve as independent markers to discriminate adolescents with IR among those with different severity of obesity. It suggests that circulating miRNA signatures might improve early identification and prevention of obesity-associated metabolic diseases in adolescents. Future studies are needed to validate these findings with larger cohorts of children in a longitudinal study.

Technical Abstract: MicroRNAs (miRNAs) are implicated in metabolic changes accompanying the progression of obesity, insulin resistance (IR), and metabolic disorders in children. Identifying circulating miRNAs that uniquely associate with these disorders may be useful in early identification and prevention of obesity-related complications. We aimed to identify circulating miRNA signatures that distinguish adolescents with obesity and IR from those with obesity unaccompanied by IR. Adolescents (aged 10-17 years) with obesity were recruited from a weight management clinic. Fasting serum samples were obtained from 33 participants. A total of 179 miRNAs was queried by a quantitative RT-PCR-based miRNA Focus Panel, and their associations with IR and body mass index (BMI) status were assessed. We found an expression pattern consisting of 12 elevated miRNAs linked to IR in obese adolescents. miR-30d, -221, and -122 were significantly correlated with clinical and biochemical markers of obesity and IR, suggestive of IR in adolescents at risk. Specific circulating miRNA signatures reflected metabolic phenotypes and predicted the presence of IR in adolescents with obesity, suggesting that miRNA indicators may identify obesity-associated complications in childhood. Further studies will be needed to understand cause versus effect and the mechanisms by which IR status links to changes in blood miRNA profiles.