MANF regulates hypothalamic control of food intake and body weight

Su Yang (), Huiming Yang, Renbao Chang, Peng Yin, Yang Yang, Weili Yang, Shanshan Huang, Marta A. Gaertig, Shihua Li () and Xiao-Jiang Li ()
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Su Yang: Emory University School of Medicine
Huiming Yang: Emory University School of Medicine
Renbao Chang: Emory University School of Medicine
Peng Yin: Emory University School of Medicine
Yang Yang: Emory University School of Medicine
Weili Yang: Jinan University
Shanshan Huang: Emory University School of Medicine
Marta A. Gaertig: Emory University School of Medicine
Shihua Li: Emory University School of Medicine
Xiao-Jiang Li: Emory University School of Medicine

Nature Communications, 2017, vol. 8, issue 1, 1-16

Abstract: 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.

Date: 2017
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DOI: 10.1038/s41467-017-00750-x

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