College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, 611130, China.
Cell Mol Life Sci. 2023 Aug 17;80(9):252. doi: 10.1007/s00018-023-04899-1.
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.
白色脂肪组织（WAT）对于调节全身能量稳态非常重要。过多的 WAT 积累进一步导致肥胖和肥胖相关疾病的发生。然而，WAT 脂质代谢重编程的更详细机制仍难以捉摸。在这里，我们报告了肥胖小鼠 WAT 和肝脏中一种环状 RNA（circRNA）mmu_circ_0001874 的异常高表达。使用特定的腺相关病毒感染靶向组织实现的 mmu_circ_0001874 干扰，下调了肥胖小鼠 WAT 和肝脏组织中的脂质积累。从机制上讲，miR-24-3p 直接与 mmu_circ_0001874 的脂质代谢效应相互作用，并通过靶向 Igf2/PI3K-AKT-mTOR 轴参与脂肪生成和脂质积累。此外，mmu_circ_0001874 与 Igf2bp2 结合以与 Ucp1 相互作用，上调 Ucp1 翻译并增加产热以减少脂质积累。总之，我们的数据强调了 circRNA 在脂质代谢重编程中的生理作用，并表明 mmu_circ_0001874/miR-24-3p/Igf2/PI3K-AKT-mTOR 和 mmu_circ_0001874/Igf2bp2/Ucp1 轴可能代表控制肥胖中脂质积累的潜在机制。
