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The melanocortin action is biased toward protection from weight loss in mice

Author

Listed:
  • Hongli Li

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

  • Yuanzhong Xu

    (University of Texas Health Science Center at Houston)

  • Yanyan Jiang

    (University of Texas Health Science Center at Houston)

  • Zhiying Jiang

    (University of Texas Health Science Center at Houston)

  • Joshua Otiz-Guzman

    (Texas Children’s Hospital)

  • Jessie C. Morrill

    (University of Texas Health Science Center at Houston
    University of Texas Health Science at Houston)

  • Jing Cai

    (University of Texas Health Science Center at Houston
    University of Texas Health Science at Houston)

  • Zhengmei Mao

    (University of Texas Health Science Center at Houston)

  • Yong Xu

    (Baylor College of Medicine, One Baylor Plaza)

  • 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
    University of Texas Health Science at Houston
    University of Texas Health Science Center at Houston)

Abstract

The melanocortin action is well perceived for its ability to regulate body weight bidirectionally with its gain of function reducing body weight and loss of function promoting obesity. However, this notion cannot explain the difficulty in identifying effective therapeutics toward treating general obesity via activation of the melanocortin action. Here, we provide evidence that altered melanocortin action is only able to cause one-directional obesity development. We demonstrate that chronic inhibition of arcuate neurons expressing proopiomelanocortin (POMC) or paraventricular hypothalamic neurons expressing melanocortin receptor 4 (MC4R) causes massive obesity. However, chronic activation of these neuronal populations failed to reduce body weight. Furthermore, gain of function of the melanocortin action through overexpression of MC4R, POMC or its derived peptides had little effect on obesity prevention or reversal. These results reveal a bias of the melanocortin action towards protection of weight loss and provide a neural basis behind the well-known, but mechanistically ill-defined, predisposition to obesity development.

Suggested Citation

  • Hongli Li & Yuanzhong Xu & Yanyan Jiang & Zhiying Jiang & Joshua Otiz-Guzman & Jessie C. Morrill & Jing Cai & Zhengmei Mao & Yong Xu & Benjamin R. Arenkiel & Cheng Huang & Qingchun Tong, 2023. "The melanocortin action is biased toward protection from weight loss in mice," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-37912-z
    DOI: 10.1038/s41467-023-37912-z
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    References listed on IDEAS

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    1. Sheng Qiu & Qinan Wu & Hao Wang & Dongfang Liu & Chen Chen & Zhiming Zhu & Hongting Zheng & Gangyi Yang & Ling Li & Mengliu Yang, 2024. "AZGP1 in POMC neurons modulates energy homeostasis and metabolism through leptin-mediated STAT3 phosphorylation," Nature Communications, Nature, vol. 15(1), pages 1-18, December.

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