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

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Abstract

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.

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Availability of data and materials

The sequencing data are available on NCBI database at Sequence Read Archive (SRA). The transcriptome sequencing data: SUB12222924.

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Acknowledgements

The authors are grateful to Ms. Ting Pan (WestChina-Frontier PharmaTech Co., Ltd, Chengdu, China) for the provision of hepatocytes.

Funding

The National Modern Agricultural Industrial Technology System (CARS-43-A-2) and the Key Research and Development Program of Sichuan Province (2021YFYZ0033) provided funding for our research.

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  1. Jiahao Shao, Meigui Wang, Anjing Zhang and Zheliang Liu contributed equally to this work.

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  1. College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, 611130, China

    Jiahao Shao, Meigui Wang, Anjing Zhang, Zheliang Liu, Genglong Jiang, Tao Tang, Jie Wang, Xianbo Jia & Songjia Lai

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The project was planned and designed by JS, JW, XJ, and SL. Data were gathered and research was carried out by JS, MW, ZL, GJ, and TT. JS and AZ wrote this paper.

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Correspondence to Songjia Lai.

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Shao, J., Wang, M., Zhang, A. et al. Interference of a mammalian circRNA regulates lipid metabolism reprogramming by targeting miR-24-3p/Igf2/PI3K-AKT-mTOR and Igf2bp2/Ucp1 axis. Cell. Mol. Life Sci. 80, 252 (2023). https://doi.org/10.1007/s00018-023-04899-1

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