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Improvement of obesity-associated disorders by a small-molecule drug targeting mitochondria of adipose tissue macrophages

Author

Listed:
  • Yawei Wang

    (Burns and Combined Injury, Third Military Medical University)

  • Binlin Tang

    (Burns and Combined Injury, Third Military Medical University
    The General Hospital of Western Theater Command)

  • Lei Long

    (Burns and Combined Injury, Third Military Medical University)

  • Peng Luo

    (Burns and Combined Injury, Third Military Medical University)

  • Wei Xiang

    (Third Military Medical University)

  • Xueru Li

    (Burns and Combined Injury, Third Military Medical University)

  • Huilan Wang

    (Burns and Combined Injury, Third Military Medical University
    Southwest Medical University)

  • Qingzhi Jiang

    (Burns and Combined Injury, Third Military Medical University
    Southwest Medical University)

  • Xu Tan

    (Burns and Combined Injury, Third Military Medical University)

  • Shenglin Luo

    (Burns and Combined Injury, Third Military Medical University)

  • Huijuan Li

    (Burns and Combined Injury, Third Military Medical University)

  • Ziwen Wang

    (Burns and Combined Injury, Third Military Medical University)

  • Zelin Chen

    (Burns and Combined Injury, Third Military Medical University)

  • Yu Leng

    (Burns and Combined Injury, Third Military Medical University)

  • Zhongyong Jiang

    (Burns and Combined Injury, Third Military Medical University)

  • Yang Wang

    (Burns and Combined Injury, Third Military Medical University)

  • Le Ma

    (Burns and Combined Injury, Third Military Medical University)

  • Rui Wang

    (Daping Hospital, Third Military Medical University)

  • Chunyu Zeng

    (Daping Hospital, Third Military Medical University)

  • Zujuan Liu

    (Burns and Combined Injury, Third Military Medical University)

  • Yu Wang

    (Burns and Combined Injury, Third Military Medical University)

  • Hongming Miao

    (Third Military Medical University)

  • Chunmeng Shi

    (Burns and Combined Injury, Third Military Medical University)

Abstract

Pro-inflammatory activation of adipose tissue macrophages (ATMs) is causally linked to obesity and obesity-associated disorders. A number of studies have demonstrated the crucial role of mitochondrial metabolism in macrophage activation. However, there is a lack of pharmaceutical agents to target the mitochondrial metabolism of ATMs for the treatment of obesity-related diseases. Here, we characterize a near-infrared fluorophore (IR-61) that preferentially accumulates in the mitochondria of ATMs and has a therapeutic effect on diet-induced obesity as well as obesity-associated insulin resistance and fatty liver. IR-61 inhibits the classical activation of ATMs by increasing mitochondrial complex levels and oxidative phosphorylation via the ROS/Akt/Acly pathway. Taken together, our findings indicate that specific enhancement of ATMs oxidative phosphorylation improves chronic inflammation and obesity-related disorders. IR-61 might be an anti-inflammatory agent useful for the treatment of obesity-related diseases by targeting the mitochondria of ATMs.

Suggested Citation

  • Yawei Wang & Binlin Tang & Lei Long & Peng Luo & Wei Xiang & Xueru Li & Huilan Wang & Qingzhi Jiang & Xu Tan & Shenglin Luo & Huijuan Li & Ziwen Wang & Zelin Chen & Yu Leng & Zhongyong Jiang & Yang Wa, 2021. "Improvement of obesity-associated disorders by a small-molecule drug targeting mitochondria of adipose tissue macrophages," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-020-20315-9
    DOI: 10.1038/s41467-020-20315-9
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