MicroRNA Crosstalk in Metabolic Disorders: The Dual Role of miR-122 and miR-34a in NAFLD and Type 2 Diabetes

NAFLD and T2DM are metabolic diseases with overlapping pathogenic mechanisms, including insulin resistance, lipid imbalance, and chronic inflammation. miRNAs have emerged as reliable biomarkers for NAFLD and T2DM. The expression levels of miRNAs hold the potential to contribute to bridging the gap between metabolic diseases. miR-122 and miR-34a are significant regulators of metabolic pathways among various biomarkers. miR-122, a liver-enriched microRNA involved in hepatic lipid metabolism, inflammation, and insulin signaling, whereas miR-34a is closely linked to β-cell dysfunction and hepatic steatosis through SIRT1 suppression. Growing echelons of these miRNAs in the bloodstream of patients with T2DM and NAFLD show their potential use as prognostic and diagnostic indicators. These enable a non-invasive early disease monitoring and detection alternative. miR-122 and miR-34a are involved in disease progression by influencing key metabolic processes such as lipid metabolism, pro-inflammatory cytokine regulation, the SIRT1-SREBP1c pathway, and AMPK phosphorylation. Their changed expression levels in various metabolic conditions contribute to advancing pathophysiological processes, explaining their clinical value as therapeutic targets. This review investigates the molecular functions of miR-122 and miR-34a in NAFLD and T2DM, emphasizing their effect on various genes and interrelated pathways, showing their diagnostic potential and therapeutic implications. Knowing their regulatory roles might lead the way for miRNA-based precision medicine techniques that improve early diagnosis, risk assessment, and treatment strategies for metabolic illnesses. Future research should focus on their therapeutic use and make targeted interventions to change their expression levels for disease management.