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A neural basis for brain leptin action on reducing type 1 diabetic hyperglycemia

Author

Listed:
  • Shengjie Fan

    (Shanghai University of Traditional Chinese Medicine
    University of Texas Health Science Center at Houston)

  • Yuanzhong Xu

    (University of Texas Health Science Center at Houston)

  • Yungang Lu

    (University of Texas Health Science Center at Houston)

  • Zhiying Jiang

    (University of Texas Health Science Center at Houston)

  • Hongli Li

    (University of Texas Health Science Center at Houston)

  • Jessie C. Morrill

    (University of Texas Health Science Center at Houston
    MD Anderson Cancer Center & UT Health Graduate School for Biomedical Sciences, University of Texas Health Science at Houston)

  • Jing Cai

    (University of Texas Health Science Center at Houston
    MD Anderson Cancer Center & UT Health Graduate School for Biomedical Sciences, University of Texas Health Science at Houston)

  • Qi Wu

    (Baylor College of Medicine, One Baylor Plaza)

  • Yong Xu

    (Baylor College of Medicine, One Baylor Plaza)

  • Mingshan Xue

    (Department of Neuroscience and Department of Molecular and Human Genetics, Baylor College of Medicine
    The Cain Foundation Laboratories, Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital)

  • Benjamin R. Arenkiel

    (Texas Children’s Hospital)

  • Cheng Huang

    (Shanghai University of Traditional Chinese Medicine)

  • Qingchun Tong

    (University of Texas Health Science Center at Houston
    MD Anderson Cancer Center & UT Health Graduate School for Biomedical Sciences, University of Texas Health Science at Houston
    University of Texas Health Science Center at Houston)

Abstract

Central leptin action rescues type 1 diabetic (T1D) hyperglycemia; however, the underlying mechanism and the identity of mediating neurons remain elusive. Here, we show that leptin receptor (LepR)-expressing neurons in arcuate (LepRArc) are selectively activated in T1D. Activation of LepRArc neurons, Arc GABAergic (GABAArc) neurons, or arcuate AgRP neurons, is able to reverse the leptin’s rescuing effect. Conversely, inhibition of GABAArc neurons, but not AgRP neurons, produces leptin-mimicking rescuing effects. Further, AgRP neuron function is not required for T1D hyperglycemia or leptin’s rescuing effects. Finally, T1D LepRArc neurons show defective nutrient sensing and signs of cellular energy deprivation, which are both restored by leptin, whereas nutrient deprivation reverses the leptin action. Our results identify aberrant activation of LepRArc neurons owing to energy deprivation as the neural basis for T1D hyperglycemia and that leptin action is mediated by inhibiting LepRArc neurons through reversing energy deprivation.

Suggested Citation

  • Shengjie Fan & Yuanzhong Xu & Yungang Lu & Zhiying Jiang & Hongli Li & Jessie C. Morrill & Jing Cai & Qi Wu & Yong Xu & Mingshan Xue & Benjamin R. Arenkiel & Cheng Huang & Qingchun Tong, 2021. "A neural basis for brain leptin action on reducing type 1 diabetic hyperglycemia," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-22940-4
    DOI: 10.1038/s41467-021-22940-4
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    Cited by:

    1. Gloria Ursino & Giorgio Ramadori & Anna Höfler & Soline Odouard & Pryscila D. S. Teixeira & Florian Visentin & Christelle Veyrat-Durebex & Giulia Lucibello & Raquel Firnkes & Serena Ricci & Claudia R., 2022. "Hepatic non-parenchymal S100A9-TLR4-mTORC1 axis normalizes diabetic ketogenesis," Nature Communications, Nature, vol. 13(1), pages 1-17, December.

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