Circular RNAs in metabolic health: bridging the gap between molecular biology and therapy

Recent advances in obesity research have shifted focus toward biological mechanisms, paralleling progress in pharmacotherapy. Fat browning-the conversion of white to brown adipocytes-emerges as a promising therapeutic strategy. Circular RNAs (circRNAs), stable non-coding RNAs with regulatory functions, are now recognized as key modulators of this process through organelle-mediated mechanisms. This review synthesizes current understanding of circRNA biogenesis and their roles in fat browning, particularly their interactions with mitochondria and endoplasmic reticulum in lipid metabolism. We highlight their capacity to encode peptides and regulate metabolic pathways, positioning circRNAs as potential precision therapeutics. While preclinical studies demonstrate mechanistic efficacy, clinical translation requires addressing delivery challenges and tissue-specific effects. This biological perspective advances obesity treatment paradigms beyond simplistic energy-balance models, mirroring the evolution seen in pharmacotherapeutic development.