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Sexual dimorphism in glucose metabolism is shaped by androgen-driven gut microbiome

Author

Listed:
  • Aibo Gao

    (Shanghai Jiao Tong University School of Medicine
    Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine)

  • Junlei Su

    (Shanghai Jiao Tong University School of Medicine
    Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine)

  • Ruixin Liu

    (Shanghai Jiao Tong University School of Medicine
    Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine)

  • Shaoqian Zhao

    (Shanghai Jiao Tong University School of Medicine
    Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine)

  • Wen Li

    (Shanghai Jiao Tong University School of Medicine
    Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine)

  • Xiaoqiang Xu

    (Aimigene Institute)

  • Danjie Li

    (Shanghai Jiao Tong University School of Medicine
    Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine)

  • Juan Shi

    (Shanghai Jiao Tong University School of Medicine
    Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine)

  • Bin Gu

    (Shanghai Jiao Tong University School of Medicine
    Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine)

  • Juan Zhang

    (Shanghai Jiao Tong University School of Medicine
    Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine)

  • Qi Li

    (CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences)

  • Xiaolin Wang

    (CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences)

  • Yifei Zhang

    (Shanghai Jiao Tong University School of Medicine
    Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine)

  • Yu Xu

    (Shanghai Jiao Tong University School of Medicine
    Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine)

  • Jieli Lu

    (Shanghai Jiao Tong University School of Medicine
    Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine)

  • Guang Ning

    (Shanghai Jiao Tong University School of Medicine
    Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine)

  • Jie Hong

    (Shanghai Jiao Tong University School of Medicine
    Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine)

  • Yufang Bi

    (Shanghai Jiao Tong University School of Medicine
    Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine)

  • Weiqiong Gu

    (Shanghai Jiao Tong University School of Medicine
    Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine)

  • Jiqiu Wang

    (Shanghai Jiao Tong University School of Medicine
    Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine)

  • Weiqing Wang

    (Shanghai Jiao Tong University School of Medicine
    Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine)

Abstract

Males are generally more susceptible to impaired glucose metabolism and type 2 diabetes (T2D) than females. However, the underlying mechanisms remain to be determined. Here, we revealed that gut microbiome depletion abolished sexual dimorphism in glucose metabolism. The transfer of male donor microbiota into antibiotics-treated female mice led the recipients to be more insulin resistant. Depleting androgen via castration changed the gut microbiome of male mice to be more similar to that of females and improved glucose metabolism, while reintroducing dihydrotestosterone (DHT) reversed these alterations. More importantly, the effects of androgen on glucose metabolism were largely abolished when the gut microbiome was depleted. Next, we demonstrated that androgen modulated circulating glutamine and glutamine/glutamate (Gln/Glu) ratio partially depending on the gut microbiome, and glutamine supplementation increases insulin sensitivity in vitro. Our study identifies the effects of androgen in deteriorating glucose homeostasis partially by modulating the gut microbiome and circulating glutamine and Gln/Glu ratio, thereby contributing to the difference in glucose metabolism between the two sexes.

Suggested Citation

  • Aibo Gao & Junlei Su & Ruixin Liu & Shaoqian Zhao & Wen Li & Xiaoqiang Xu & Danjie Li & Juan Shi & Bin Gu & Juan Zhang & Qi Li & Xiaolin Wang & Yifei Zhang & Yu Xu & Jieli Lu & Guang Ning & Jie Hong &, 2021. "Sexual dimorphism in glucose metabolism is shaped by androgen-driven gut microbiome," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-27187-7
    DOI: 10.1038/s41467-021-27187-7
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    References listed on IDEAS

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