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Paraventricular hypothalamic RUVBL2 neurons suppress appetite by enhancing excitatory synaptic transmission in distinct neurocircuits

Author

Listed:
  • Mingming Xing

    (Tianjin Medical University)

  • Yang Li

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Yuqi Zhang

    (Tianjin Medical University)

  • Juemou Zhou

    (Tianjin Medical University)

  • Danting Ma

    (Tianjin Medical University)

  • Mengqi Zhang

    (Tianjin Medical University)

  • Minglei Tang

    (Tianjin Medical University)

  • Ting Ouyang

    (Tianjin Medical University)

  • Fumiao Zhang

    (Tianjin Medical University)

  • Xiaofeng Shi

    (Tianjin Medical University)

  • Jianyuan Sun

    (University of Chinese Academy of Sciences
    Chinese Academy of Sciences)

  • Zuxin Chen

    (Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions)

  • Weiping J. Zhang

    (Tianjin Medical University)

  • Shuli Zhang

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Xiangyang Xie

    (Tianjin Medical University)

Abstract

The paraventricular hypothalamus (PVH) is crucial for food intake control, yet the presynaptic mechanisms underlying PVH neurons remain unclear. Here, we show that RUVBL2 in the PVH is significantly reduced during energy deficit, and knockout (KO) of PVH RUVBL2 results in hyperphagic obesity in mice. RUVBL2-expressing neurons in the PVH (PVHRUVBL2) exert the anorexigenic effect by projecting to the arcuate hypothalamus, the dorsomedial hypothalamus, and the parabrachial complex. We further demonstrate that PVHRUVBL2 neurons form the synaptic connections with POMC and AgRP neurons in the ARC. PVH RUVBL2 KO impairs the excitatory synaptic transmission by reducing presynaptic boutons and synaptic vesicles near active zone. Finally, RUVBL2 overexpression in the PVH suppresses food intake and protects against diet induced obesity. Together, this study demonstrates an essential role for PVH RUVBL2 in food intake control, and suggests that modulation of synaptic plasticity could be an effective way to curb appetite and obesity.

Suggested Citation

  • Mingming Xing & Yang Li & Yuqi Zhang & Juemou Zhou & Danting Ma & Mengqi Zhang & Minglei Tang & Ting Ouyang & Fumiao Zhang & Xiaofeng Shi & Jianyuan Sun & Zuxin Chen & Weiping J. Zhang & Shuli Zhang &, 2024. "Paraventricular hypothalamic RUVBL2 neurons suppress appetite by enhancing excitatory synaptic transmission in distinct neurocircuits," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-53258-6
    DOI: 10.1038/s41467-024-53258-6
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