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Adipocyte-derived kynurenine promotes obesity and insulin resistance by activating the AhR/STAT3/IL-6 signaling

Author

Listed:
  • Teng Huang

    (Huazhong University of Science and Technology)

  • Jia Song

    (Huazhong University of Science and Technology
    Huazhong University of Science and Technology)

  • Jia Gao

    (Huazhong University of Science and Technology)

  • Jia Cheng

    (Huazhong University of Science and Technology
    Huazhong University of Science and Technology)

  • Hao Xie

    (Huazhong University of Science and Technology)

  • Lu Zhang

    (Huazhong University of Science and Technology)

  • Yu-Han Wang

    (Huazhong University of Science and Technology)

  • Zhichao Gao

    (Huazhong University of Science and Technology)

  • Yi Wang

    (Huazhong University of Science and Technology)

  • Xiaohui Wang

    (Huazhong University of Science and Technology)

  • Jinhan He

    (West China Hospital, Sichuan University)

  • Shiwei Liu

    (Third Hospital of Shanxi Medical University)

  • Qilin Yu

    (Huazhong University of Science and Technology)

  • Shu Zhang

    (Huazhong University of Science and Technology)

  • Fei Xiong

    (Huazhong University of Science and Technology)

  • Qing Zhou

    (Huazhong University of Science and Technology)

  • Cong-Yi Wang

    (Huazhong University of Science and Technology)

Abstract

Aberrant amino acid metabolism is a common event in obesity. Particularly, subjects with obesity are characterized by the excessive plasma kynurenine (Kyn). However, the primary source of Kyn and its impact on metabolic syndrome are yet to be fully addressed. Herein, we show that the overexpressed indoleamine 2,3-dioxygenase 1 (IDO1) in adipocytes predominantly contributes to the excessive Kyn, indicating a central role of adipocytes in Kyn metabolism. Depletion of Ido1 in adipocytes abrogates Kyn accumulation, protecting mice against obesity. Mechanistically, Kyn impairs lipid homeostasis in adipocytes via activating the aryl hydrocarbon receptor (AhR)/Signal transducer and activator of transcription 3 /interleukin-6 signaling. Genetic ablation of AhR in adipocytes abolishes the effect of Kyn. Moreover, supplementation of vitamin B6 ameliorated Kyn accumulation, protecting mice from obesity. Collectively, our data support that adipocytes are the primary source of increased circulating Kyn, while elimination of accumulated Kyn could be a viable strategy against obesity.

Suggested Citation

  • Teng Huang & Jia Song & Jia Gao & Jia Cheng & Hao Xie & Lu Zhang & Yu-Han Wang & Zhichao Gao & Yi Wang & Xiaohui Wang & Jinhan He & Shiwei Liu & Qilin Yu & Shu Zhang & Fei Xiong & Qing Zhou & Cong-Yi , 2022. "Adipocyte-derived kynurenine promotes obesity and insulin resistance by activating the AhR/STAT3/IL-6 signaling," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31126-5
    DOI: 10.1038/s41467-022-31126-5
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    Cited by:

    1. Xiuchuan (Lucas) Hu & Wenfeng Xiao & Yuxian Lei & Adam Green & Xinyi Lee & Muralidhara Rao Maradana & Yajing Gao & Xueru Xie & Rui Wang & George Chennell & M. Albert Basson & Pete Kille & Wolfgang Mar, 2023. "Aryl hydrocarbon receptor utilises cellular zinc signals to maintain the gut epithelial barrier," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

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