MicroRNAs in Obesity-Associated Metabolic Inflammation: From Molecular Mechanisms to Clinical Translation.

Metabolic inflammation, triggered by obesity is a core pathological link in complications such as type 2 diabetes, cardiovascular diseases, and non-alcoholic fatty liver disease. This review explains the central hub role of microRNAs in obesity-related chronic low-grade inflammation, achieved through their precise regulation of macrophage polarisation, inflammatory signalling pathways, and adipokine secretion. Importantly, this relationship is bidirectional-while miRNAs regulate inflammatory cascades, the inflammatory environment itself can alter miRNA expression, forming complex feedback loops. Circulating miRNAs, due to their stability (conferred by encapsulation in exosomes or binding to proteins), tissue specificity, and strong correlation with pathological processes, show great potential as promising non-invasive biomarkers for metabolic inflammation, useful for assessing its activity and complication risk. Furthermore, miRNA-based intervention strategies have demonstrated significant metabolic improvements in animal models. However, their clinical translation still faces challenges such as insufficient delivery targeting, off-target effects, and pharmacokinetic defects. This article aims to summarise the regulatory network of miRNAs in metabolic inflammation and discuss in depth their potential and the bottlenecks to be solved for moving from basic research to clinical application, providing new theoretical basis and strategic directions for the diagnosis and targeted therapy of obesity-related metabolic diseases.