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Author Notes:

Correspondence and requests for materials should be addressed to S.Y. (email: syang33@emory.edu) or to S.L. (email: sli@emory.edu) or to X.-J.L. (email: xli2@emory.edu)

S.Y. designed and performed experiments, analyzed data and wrote the paper.

H.Y., R.C., P.Y., Y.Y., W.Y. and S.H. performed experiments.

M.A.G. assisted with mouse breeding.

S.L. and X.-J.L. designed experiments, analyzed data and wrote and edited the paper.

We thank Vanderbilt Mouse Metabolic Phenotyping Center (DK059637) for performing indirect calorimetry, Dr. Feng Zhang for his contribution of CRISPR related plasmids, and Grace Wynn for her help with mouse behavioral tests.

The authors declare no competing financial interests.

Subjects:

Research Funding:

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:

  • Science & Technology
  • Multidisciplinary Sciences
  • Science & Technology - Other Topics
  • NERVOUS-SYSTEM CONTROL
  • NEUROTROPHIC FACTOR
  • ENDOPLASMIC-RETICULUM
  • ENERGY HOMEOSTASIS
  • SELECTIVE DELETION
  • INSULIN-RESISTANCE
  • GLUCOSE-PRODUCTION
  • PROTEIN RESPONSE
  • SCA17 MICE
  • OBESITY

MANF regulates hypothalamic control of food intake and body weight

Tools:

Journal Title:

Nature Communications

Volume:

Volume 8, Number 1

Publisher:

, Pages 579-579

Type of Work:

Article | Final Publisher PDF

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.

Copyright information:

© 2017 The Author(s).

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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