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Secretin-dependent signals in the ventromedial hypothalamus regulate energy metabolism and bone homeostasis in mice

Author

Listed:
  • Fengwei Zhang

    (the University of Hong Kong)

  • Wei Qiao

    (the University of Hong Kong
    the University of Hong Kong-Shenzhen Hospital)

  • Ji-an Wei

    (the University of Hong Kong
    Jinan University)

  • Zhengyi Tao

    (the University of Hong Kong)

  • Congjia Chen

    (the University of Hong Kong)

  • Yefeng Wu

    (the University of Hong Kong)

  • Minghui Lin

    (the University of Hong Kong)

  • Ka Man Carmen Ng

    (the University of Hong Kong)

  • Li Zhang

    (Jinan University
    University of Health and Rehabilitation Sciences)

  • Kelvin Wai-Kwok Yeung

    (the University of Hong Kong-Shenzhen Hospital
    the University of Hong Kong)

  • Billy Kwok Chong Chow

    (the University of Hong Kong)

Abstract

Secretin, though originally discovered as a gut-derived hormone, is recently found to be abundantly expressed in the ventromedial hypothalamus, from which the central neural system controls satiety, energy metabolism, and bone homeostasis. However, the functional significance of secretin in the ventromedial hypothalamus remains unclear. Here we show that the loss of ventromedial hypothalamus-derived secretin leads to osteopenia in male and female mice, which is primarily induced by diminished cAMP response element-binding protein phosphorylation and upregulation in peripheral sympathetic activity. Moreover, the ventromedial hypothalamus-secretin inhibition also contributes to hyperphagia, dysregulated lipogenesis, and impaired thermogenesis, resulting in obesity in male and female mice. Conversely, overexpression of secretin in the ventromedial hypothalamus promotes bone mass accrual in mice of both sexes. Collectively, our findings identify an unappreciated secretin signaling in the central neural system for the regulation of energy and bone metabolism, which may serve as a new target for the clinical management of obesity and osteoporosis.

Suggested Citation

  • Fengwei Zhang & Wei Qiao & Ji-an Wei & Zhengyi Tao & Congjia Chen & Yefeng Wu & Minghui Lin & Ka Man Carmen Ng & Li Zhang & Kelvin Wai-Kwok Yeung & Billy Kwok Chong Chow, 2024. "Secretin-dependent signals in the ventromedial hypothalamus regulate energy metabolism and bone homeostasis in mice," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-45436-3
    DOI: 10.1038/s41467-024-45436-3
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    References listed on IDEAS

    as
    1. Hao Chen & Bo Hu & Xiao Lv & Shouan Zhu & Gehua Zhen & Mei Wan & Amit Jain & Bo Gao & Yu Chai & Mi Yang & Xiao Wang & Ruoxian Deng & Lei Wang & Yong Cao & Shuangfei Ni & Shen Liu & Wen Yuan & Huajiang, 2019. "Prostaglandin E2 mediates sensory nerve regulation of bone homeostasis," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
    2. Wei Qiao & Dayu Pan & Yufeng Zheng & Shuilin Wu & Xuanyong Liu & Zhuofan Chen & Mei Wan & Shiqin Feng & Kenneth M. C. Cheung & Kelvin W. K. Yeung & Xu Cao, 2022. "Divalent metal cations stimulate skeleton interoception for new bone formation in mouse injury models," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
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