MANF regulates hypothalamic control of food intake and body weight

• Type of Material: Article
• Authors: Su Yang, Emory University; Huiming Yang, Emory University; Renbao Chang, Emory University; Peng Yin, Emory University; Yang Yang, Emory University; Weili Yang, Jinan University; Shanshan Huang, Emory University; Marta A. Gaertig, Emory University; Shi Hua Li, Emory University; Xiao-Jiang Li, Emory University
• Language: English
• Date: 2017-09-18
• Publisher: Nature Publishing Group
• Publication Version: Final Published Version
• Copyright Statement: © 2017 The Author(s).
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/s41467-017-00750-x
• Title of Journal or Parent Work: Nature Communications
• ISSN: 2041-1723
• Volume: 8
• Issue: 1
• Start Page: 579
• End Page: 579
• Grant/Funding Information: The work was supported by NIH grants (NS102913-01, NS101701-01 to X.-J.L. and NS095279 to S.L.) and the National Natural Science Foundation of China (91332206, 81461148020).; This research project was supported in part by the Viral Vector Core and the Emory University Integrated Proteomics Core of the Emory Neuroscience NINDS Core Facilities grant, P30NS055077.
• Keywords: PROTEIN RESPONSE; Multidisciplinary Sciences; NEUROTROPHIC FACTOR; ENERGY HOMEOSTASIS; Science & Technology; INSULIN-RESISTANCE; SCA17 MICE; SELECTIVE DELETION; GLUCOSE-PRODUCTION; NERVOUS-SYSTEM CONTROL; OBESITY; ENDOPLASMIC-RETICULUM; Science & Technology - Other Topics
• Research Categories: Biology, Genetics; Biology, Neuroscience

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.