Format

Send to

Choose Destination
Nat Commun. 2017 Sep 18;8(1):579. doi: 10.1038/s41467-017-00750-x.

MANF regulates hypothalamic control of food intake and body weight.

Author information

1
Department of Human Genetics, Emory University School of Medicine, 615 Michael Street, Room 355, Atlanta, GA, 30322, USA. syang33@emory.edu.
2
Department of Human Genetics, Emory University School of Medicine, 615 Michael Street, Room 355, Atlanta, GA, 30322, USA.
3
Department of Neurology, Xiangya Hospital, Central South University, Changsha, 410008, China.
4
GHM Institute of CNS Regeneration, Jinan University, Guangzhou, 510631, China.
5
Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430032, China.
6
Department of Human Genetics, Emory University School of Medicine, 615 Michael Street, Room 355, Atlanta, GA, 30322, USA. sli@emory.edu.
7
GHM Institute of CNS Regeneration, Jinan University, Guangzhou, 510631, China. sli@emory.edu.
8
Department of Human Genetics, Emory University School of Medicine, 615 Michael Street, Room 355, Atlanta, GA, 30322, USA. xli2@emory.edu.
9
GHM Institute of CNS Regeneration, Jinan University, Guangzhou, 510631, China. xli2@emory.edu.

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.MANF is a neurotrophic factor that is secreted but also mediates the unfolded protein response acting intracellularly. Here, the authors show that MANF expression in the brain is influenced by nutritional cues, and hypothalamic MANF influences food intake and systemic energy homeostasis.

PMID:
28924165
PMCID:
PMC5603516
DOI:
10.1038/s41467-017-00750-x
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center