Background: Obesity will cause metabolic syndrome (Mets) easily, and its pathogenesis is not completely clear.

Aim: To probe into the predictive value of miR-122-5p and its regulatory mechanism in Mets.

Method: The predictive effect of miR-122-5p on Mets was evaluated by constructing a Receiver Operating Characteristic (ROC) curve. The target genes of miR-122-5p were predicted using the ENCORI/starBase and TargetScanHuman databases, and pyruvate kinase M2 (PKM2), closely related to Mets, was screened by GO and KEGG analysis. The roles of miR-122-5p/PKM2 in insulin resistance (IR) were explored by treating the human normal liver cells (HLCs) with palmitic acid (PA) to induce the IR model. The effects of miR-122-5p/PKM2 on glucose metabolism (GM) of HLCs were evaluated by detecting the production of pyruvic acid, lactic acid, and ATP.

Results: MiR-122-5p was highly expressed in obese people and Mets patients, and its predicted AUC for Mets was 0.876. In HLCs transfected with wild-type PKM2 luciferase vector (PKM2-wt), luciferase activity was attenuated by the miR-122-5p mimic and enhanced by its inhibitor. The expression of PKM2 was inhibited by the miR-122-5p mimic and up-regulated by its inhibitor. The miR-122-5p mimic enhanced PA-induced IR and inhibited the GM of HLCs, which were reversed by overexpression of PKM2. The miR-122-5p inhibitor exerted the opposite effects of its mimic, which were also reversed by silencing of PKM2.

Conclusion: MiR-122-5p, a risk factor for Mets, mediated the IR and abnormal glucose metabolism of HLCs by negatively regulating PKM2.

Clinical trial number: Not applicable.

Keywords: Glucose metabolism; Insulin resistance; Metabolic syndrome; Obesity; PKM2; miR-122-5p.

© 2025. The Author(s).