1. Neuroscience
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High-fat diet enhances starvation-induced hyperactivity via sensitizing hunger-sensing neurons in Drosophila

  1. Rui Huang  Is a corresponding author
  2. Tingting Song
  3. Haifeng Su
  4. Zeliang Lai
  5. Wusa Qin
  6. Yinjun Tian
  7. Xuan Dong
  8. Liming Wang  Is a corresponding author
  1. Chongqing University, China
  2. Shenzhen Bay Laboratory, China
  3. Institute of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, China
  4. Zhejiang University, China
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Cite this article as: eLife 2020;9:e53103 doi: 10.7554/eLife.53103

Abstract

The function of the central nervous system to regulate food intake can be disrupted by sustained metabolic challenges such as high-fat diet (HFD), which may contribute to various metabolic disorders. Previously, we showed that a group of octopaminergic (OA) neurons mediated starvation-induced hyperactivity, an important aspect of food-seeking behavior (Yu et al., 2016). Here we find that HFD specifically enhances this behavior. Mechanistically, HFD increases the excitability of these OA neurons to a hunger hormone named adipokinetic hormone (AKH), via increasing the accumulation of AKH receptor (AKHR) in these neurons. Upon HFD, excess dietary lipids are transported by a lipoprotein LTP to enter these OA+AKHR+ neurons via the cognate receptor LpR1, which in turn suppresses autophagy-dependent degradation of AKHR. Taken together, we uncover a mechanism that links HFD, neuronal autophagy, and starvation-induced hyperactivity, providing insight in the reshaping of neural circuitry under metabolic challenges and the progression of metabolic diseases.

Data availability

Sequencing data have been deposited in GEO under accession codes GSE129601 and GSE129602.All behavioral data are uploaded in Supplementary Data File 1.Mass spectrometry data is updated in Supplementary Data File 2.

The following data sets were generated

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Author details

  1. Rui Huang

    Chongqing University, Chongqing, China
    For correspondence
    huangrui85@cqu.edu.cn
    Competing interests
    The authors declare that no competing interests exist.

  2. Tingting Song

    Shenzhen Bay Laboratory, Shenzhen, China
    Competing interests
    The authors declare that no competing interests exist.

  3. Haifeng Su

    Institute of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.

  4. Zeliang Lai

    Shenzhen Bay Laboratory, Shenzhen, China
    Competing interests
    The authors declare that no competing interests exist.

  5. Wusa Qin

    Shenzhen Bay Laboratory, Shenzhen, China
    Competing interests
    The authors declare that no competing interests exist.

  6. Yinjun Tian

    Life Sciences Institute, Zhejiang University, Hangzhou, China
    Competing interests
    The authors declare that no competing interests exist.

  7. Xuan Dong

    Life Sciences Institute, Zhejiang University, Hangzhou, China
    Competing interests
    The authors declare that no competing interests exist.

  8. Liming Wang

    Life Sciences Institute, Zhejiang University, Hangzhou, China
    For correspondence
    lmwang83@zju.edu.cn
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7256-8776

Funding

National Natural Science Foundation of China (31522026)

  • Liming Wang

National Natural Science Foundation of China (31800883)

  • Rui Huang

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. K VijayRaghavan, National Centre for Biological Sciences, Tata Institute of Fundamental Research, India

Publication history

  1. Received: October 30, 2019
  2. Accepted: April 22, 2020
  3. Accepted Manuscript published: April 23, 2020 (version 1)
  4. Version of Record published: June 5, 2020 (version 2)

Copyright

© 2020, Huang et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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