MANF regulates hypothalamic control of food intake and body weight

作者：Yang, Su; Yang, Huiming; Chang, Renbao; Yin, Peng; Yang, Yang; Yang, Weili; Huang, Shanshan; Gaertig, Marta A.; Li, Shihua^*; Li, Xiao-Jiang^*

来源：Nature Communications, 2017, 8(1): 579.

DOI：10.1038/s41467-017-00750-x

• NERVOUS-SYSTEM CONTROL
• NEUROTROPHIC FACTOR
• ENDOPLASMIC-RETICULUM
• ENERGY HOMEOSTASIS
• SELECTIVE DELETION
• INSULIN-RESISTANCE
• GLUCOSE-PRODUCTION
• PROTEIN RESPONSE
• SCA17 MICE
• OBESITY

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.

• 出版日期2017-9-18
• 单位中南大学; 暨南大学; 华中科技大学