Interference of a mammalian circRNA regulates lipid metabolism reprogramming by targeting miR-24-3p/Igf2/PI3K-AKT-mTOR and Igf2bp2/Ucp1 axis

• DOI: 10.1007/s00018-023-04899-1
• Publication Date: 2023-08-17T02:02:32Z
• Authors: Jiahao Shao; Meigui Wang; Anjing Zhang; Zheliang Liu; Genglong Jiang; Tao Tang; Jie Wang; Xianbo Jia; Songjia Lai
• Keywords: 2. Zero hunger; Mice; MicroRNAs; Phosphatidylinositol 3-Kinases; TOR Serine-Threonine Kinases; Animals; Obesity; RNA, Circular; Lipid Metabolism; Lipids; Proto-Oncogene Proteins c-akt; Uncoupling Protein 1

White adipose tissue (WAT) is important for regulating the whole systemic energy homeostasis. Excessive WAT accumulation further contributes to the development of obesity and obesity-related illnesses. More detailed mechanisms for WAT lipid metabolism reprogramming, however, are still elusive. Here, we report the abnormally high expression of a circular RNA (circRNA) mmu_circ_0001874 in the WAT and liver of mice with obesity. mmu_circ_0001874 interference achieved using a specific adeno-associated virus infects target tissues, down-regulating lipid accumulation in the obesity mice WAT, and liver tissues. Mechanistically, miR-24-3p directly interacts with the lipid metabolism effect of mmu_circ_0001874 and participates in adipogenesis and lipid accumulation by targeting Igf2/PI3K-AKT-mTOR axis. Moreover, mmu_circ_0001874 binds to Igf2bp2 to interact with Ucp1, up-regulating Ucp1 translation and increasing thermogenesis to decrease lipid accumulation. In conclusion, our data highlight a physiological role for circRNA in lipid metabolism reprogramming and suggest mmu_circ_0001874/miR-24-3p/Igf2/PI3K-AKT-mTOR and mmu_circ_0001874/Igf2bp2/Ucp1 axis may represent a potential mechanism for controlling lipid accumulation in obesity.