The hypothalamus has a vital role in controlling food intake and energy homeostasis; its activity is modulated by neuropeptides and endocrine factors. Mesencephalic astrocytederived 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.
基金：
NIH [NS102913-01, NS101701-01, NS095279]; National Natural Science Foundation of China [91332206, 81461148020]; Viral Vector Core of the Emory Neuroscience NINDS Core Facilities grant [P30NS055077]; Emory University Integrated Proteomics Core of the Emory Neuroscience NINDS Core Facilities grant [P30NS055077]
第一作者单位：[1]Emory Univ, Sch Med, Dept Human Genet, 615 Michael St,Room 355, Atlanta, GA 30322 USA
通讯作者：
通讯机构：[1]Emory Univ, Sch Med, Dept Human Genet, 615 Michael St,Room 355, Atlanta, GA 30322 USA[3]Jinan Univ, GHM Inst CNS Regenerat, Guangzhou 510631, Guangdong, Peoples R China
推荐引用方式(GB/T 7714)：
Yang Su,Yang Huiming,Chang Renbao,et al.MANF regulates hypothalamic control of food intake and body weight[J].NATURE COMMUNICATIONS.2017,8:doi:10.1038/s41467-017-00750-x.
APA：
Yang, Su,Yang, Huiming,Chang, Renbao,Yin, Peng,Yang, Yang...&Li, Xiao-Jiang.(2017).MANF regulates hypothalamic control of food intake and body weight.NATURE COMMUNICATIONS,8,
MLA：
Yang, Su,et al."MANF regulates hypothalamic control of food intake and body weight".NATURE COMMUNICATIONS 8.(2017)
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