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Lipopolysaccharide binding protein resists hepatic oxidative stress by regulating lipid droplet homeostasis

Author

Listed:
  • Qilun Zhang

    (University of Science and Technology of China)

  • Xuting Shen

    (Anhui Medical University)

  • Xin Yuan

    (Anhui Medical University)

  • Jing Huang

    (Anhui Medical University)

  • Yaling Zhu

    (Anhui Medical University)

  • Tengteng Zhu

    (Anhui Medical University)

  • Tao Zhang

    (Anhui Medical University)

  • Haibo Wu

    (University of Science and Technology of China)

  • Qian Wu

    (The First Affiliated Hospital of Anhui University of Chinese Medicine)

  • Yinguang Fan

    (Anhui Medical University)

  • Jing Ni

    (Anhui Medical University)

  • Leilei Meng

    (Anhui Medical University)

  • Anyuan He

    (Anhui Medical University)

  • Chaowei Shi

    (University of Science and Technology of China)

  • Hao Li

    (University of Science and Technology of China)

  • Qingsong Hu

    (University of Science and Technology of China)

  • Jian Wang

    (Beijing Institute of Lifeomics)

  • Cheng Chang

    (Beijing Institute of Lifeomics)

  • Fan Huang

    (First Affiliated Hospital of Anhui Medical University)

  • Fang Li

    (First Affiliated Hospital of Anhui Medical University)

  • Meng Chen

    (Graduate School of Bengbu Medical College)

  • Anding Liu

    (Huazhong University of Science and Technology)

  • Shandong Ye

    (University of Science and Technology of China)

  • Mao Zheng

    (University of Science and Technology of China)

  • Haoshu Fang

    (Anhui Medical University)

Abstract

Oxidative stress-induced lipid accumulation is mediated by lipid droplets (LDs) homeostasis, which sequester vulnerable unsaturated triglycerides into LDs to prevent further peroxidation. Here we identify the upregulation of lipopolysaccharide-binding protein (LBP) and its trafficking through LDs as a mechanism for modulating LD homeostasis in response to oxidative stress. Our results suggest that LBP induces lipid accumulation by controlling lipid-redox homeostasis through its lipid-capture activity, sorting unsaturated triglycerides into LDs. N-acetyl-L-cysteine treatment reduces LBP-mediated triglycerides accumulation by phospholipid/triglycerides competition and Peroxiredoxin 4, a redox state sensor of LBP that regulates the shuttle of LBP from LDs. Furthermore, chronic stress upregulates LBP expression, leading to insulin resistance and obesity. Our findings contribute to the understanding of the role of LBP in regulating LD homeostasis and against cellular peroxidative injury. These insights could inform the development of redox-based therapies for alleviating oxidative stress-induced metabolic dysfunction.

Suggested Citation

  • Qilun Zhang & Xuting Shen & Xin Yuan & Jing Huang & Yaling Zhu & Tengteng Zhu & Tao Zhang & Haibo Wu & Qian Wu & Yinguang Fan & Jing Ni & Leilei Meng & Anyuan He & Chaowei Shi & Hao Li & Qingsong Hu &, 2024. "Lipopolysaccharide binding protein resists hepatic oxidative stress by regulating lipid droplet homeostasis," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-47553-5
    DOI: 10.1038/s41467-024-47553-5
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    References listed on IDEAS

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    1. Chi Ma & Aparna H. Kesarwala & Tobias Eggert & José Medina-Echeverz & David E. Kleiner & Ping Jin & David F. Stroncek & Masaki Terabe & Veena Kapoor & Mei ElGindi & Miaojun Han & Angela M. Thornton & , 2016. "NAFLD causes selective CD4+ T lymphocyte loss and promotes hepatocarcinogenesis," Nature, Nature, vol. 531(7593), pages 253-257, March.
    2. Robert S. Jack & Xiaolong Fan & Martin Bernheiden & Gabriele Rune & Monika Ehlers & Albert Weber & Gerhard Kirsch & Renate Mentel & Birgit Fürll & Marina Freudenberg & Gerd Schmitz & Felix Stelter & C, 1997. "Lipopolysaccharide-binding protein is required to combat a murine Gram-negative bacterial infection," Nature, Nature, vol. 389(6652), pages 742-745, October.
    3. Chenxu Ge & Jun Tan & Xianling Dai & Qin Kuang & Shaoyu Zhong & Lili Lai & Chao Yi & Yan Sun & Jing Luo & Chufeng Zhang & Liancai Zhu & Bochu Wang & Minxuan Xu, 2022. "Hepatocyte phosphatase DUSP22 mitigates NASH-HCC progression by targeting FAK," Nature Communications, Nature, vol. 13(1), pages 1-21, December.
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