Circular RNAs in obesity and related metabolic disorders: mechanistic insights and therapeutic perspectives.

Obesity is a multifactorial and chronic metabolic disease strongly linked to type 2 diabetes mellitus, non-alcoholic fatty liver disease, cardiovascular complications, and several cancers. Despite advances in pharmacological and surgical interventions, long-term management remains suboptimal, emphasizing the need for new molecular targets. Circular RNAs (circRNAs), a unique class of covalently closed non-coding RNAs, have recently emerged as critical regulators of metabolic homeostasis. By acting as microRNA sponges, transcriptional modulators, and protein scaffolds, circRNAs participate in key processes such as adipogenesis, lipid metabolism, inflammation, and insulin signaling. Dysregulated circRNA expression has been implicated in obesity-induced β-cell dysfunction, hepatic steatosis, vascular remodeling, and tumor progression. Their high stability, evolutionary conservation, and tissue-specific expression further highlight their promise as minimally invasive biomarkers and therapeutic candidates for obesity-associated disorders. However, translation to clinical application remains limited due to methodological inconsistencies, lack of standardized quantification, and insufficient functional validation. Future integration of circRNA profiling with multi-omics and genome-editing approaches could accelerate the identification of mechanistic pathways and therapeutic targets, paving the way for precision medicine strategies in obesity and related metabolic diseases.