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Surplus fatty acid synthesis increases oxidative stress in adipocytes and induces lipodystrophy

Author

Listed:
  • Li Weng

    (Fudan University
    Xiamen University)

  • Wen-Shuai Tang

    (Fudan University)

  • Xu Wang

    (School of Life Science, Anhui Medical University, Research Center for Translational Medicine, the Second Affiliated Hospital of Anhui Medical University)

  • Yingyun Gong

    (the First Affiliated Hospital of Nanjing Medical University)

  • Changqin Liu

    (the First Affiliated Hospital, Xiamen University, Xiamen)

  • Ni-Na Hong

    (Xiamen University)

  • Ying Tao

    (Fudan University)

  • Kuang-Zheng Li

    (Fudan University)

  • Shu-Ning Liu

    (Optogenetics & Synthetic Biology Interdisciplinary Research Center, Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology)

  • Wanzi Jiang

    (the First Affiliated Hospital of Nanjing Medical University)

  • Ying Li

    (Northern Jiangsu People’s Hospital)

  • Ke Yao

    (Tsinghua University)

  • Li Chen

    (Fudan University)

  • He Huang

    (Fudan University)

  • Yu-Zheng Zhao

    (Optogenetics & Synthetic Biology Interdisciplinary Research Center, Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology)

  • Ze-Ping Hu

    (Tsinghua University)

  • Youli Lu

    (Shanghai Engineering Research Center of Phase I Clinical Research & Quality Consistency Evaluation for Drugs, Institute of Clinical Mass Spectrometry, Shanghai Academy of Experimental Medicine)

  • Haobin Ye

    (Fudan University)

  • Xingrong Du

    (Fudan University)

  • Hongwen Zhou

    (the First Affiliated Hospital of Nanjing Medical University)

  • Peng Li

    (Fudan University
    Zhengzhou University)

  • Tong-Jin Zhao

    (Fudan University
    Zhengzhou University)

Abstract

Adipocytes are the primary sites for fatty acid storage, but the synthesis rate of fatty acids is very low. The physiological significance of this phenomenon remains unclear. Here, we show that surplus fatty acid synthesis in adipocytes induces necroptosis and lipodystrophy. Transcriptional activation of FASN elevates fatty acid synthesis, but decreases NADPH level and increases ROS production, which ultimately leads to adipocyte necroptosis. We identify MED20, a subunit of the Mediator complex, as a negative regulator of FASN transcription. Adipocyte-specific male Med20 knockout mice progressively develop lipodystrophy, which is reversed by scavenging ROS. Further, in a murine model of HIV-associated lipodystrophy and a human patient with acquired lipodystrophy, ROS neutralization significantly improves metabolic disorders, indicating a causal role of ROS in disease onset. Our study well explains the low fatty acid synthesis rate in adipocytes, and sheds light on the management of acquired lipodystrophy.

Suggested Citation

  • Li Weng & Wen-Shuai Tang & Xu Wang & Yingyun Gong & Changqin Liu & Ni-Na Hong & Ying Tao & Kuang-Zheng Li & Shu-Ning Liu & Wanzi Jiang & Ying Li & Ke Yao & Li Chen & He Huang & Yu-Zheng Zhao & Ze-Ping, 2024. "Surplus fatty acid synthesis increases oxidative stress in adipocytes and induces lipodystrophy," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-023-44393-7
    DOI: 10.1038/s41467-023-44393-7
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    References listed on IDEAS

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