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MANF regulates hypothalamic control of food intake and body weight

Author

Listed:
  • Su Yang

    (Emory University School of Medicine)

  • Huiming Yang

    (Emory University School of Medicine
    Central South University)

  • Renbao Chang

    (Emory University School of Medicine)

  • Peng Yin

    (Emory University School of Medicine)

  • Yang Yang

    (Emory University School of Medicine
    Central South University)

  • Weili Yang

    (Jinan University)

  • Shanshan Huang

    (Emory University School of Medicine
    Huazhong University of Science and Technology)

  • Marta A. Gaertig

    (Emory University School of Medicine)

  • Shihua Li

    (Emory University School of Medicine
    Jinan University)

  • Xiao-Jiang Li

    (Emory University School of Medicine
    Jinan University)

Abstract

The hypothalamus has a vital role in controlling food intake and energy homeostasis; its activity is modulated by neuropeptides and endocrine factors. Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a neurotrophic factor that is also localized in the endoplasmic reticulum (ER) in neurons. Here we show that MANF is highly enriched in distinct nuclei of the mouse hypothalamus, and that MANF expression in the hypothalamus is upregulated in response to fasting. Increasing or decreasing hypothalamic MANF protein levels causes hyperphagia or hypophagia, respectively. Moreover, MANF triggers hypothalamic insulin resistance by enhancing the ER localization and activity of PIP4k2b, a kinase known to regulate insulin signaling. Our findings indicate that MANF influences food intake and body weight by modulating hypothalamic insulin signaling.

Suggested Citation

  • Su Yang & Huiming Yang & Renbao Chang & Peng Yin & Yang Yang & Weili Yang & Shanshan Huang & Marta A. Gaertig & Shihua Li & Xiao-Jiang Li, 2017. "MANF regulates hypothalamic control of food intake and body weight," Nature Communications, Nature, vol. 8(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00750-x
    DOI: 10.1038/s41467-017-00750-x
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