1. Neuroscience

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
https://doi.org/10.7554/eLife.53103
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Cite this article
  1. Rui Huang
  2. Tingting Song
  3. Haifeng Su
  4. Zeliang Lai
  5. Wusa Qin
  6. Yinjun Tian
  7. Xuan Dong
  8. Liming Wang
(2020)
High-fat diet enhances starvation-induced hyperactivity via sensitizing hunger-sensing neurons in Drosophila
eLife 9:e53103.
https://doi.org/10.7554/eLife.53103
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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.

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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  1. Rui Huang
  2. Tingting Song
  3. Haifeng Su
  4. Zeliang Lai
  5. Wusa Qin
  6. Yinjun Tian
  7. Xuan Dong
  8. Liming Wang
(2020)
High-fat diet enhances starvation-induced hyperactivity via sensitizing hunger-sensing neurons in Drosophila
eLife 9:e53103.
https://doi.org/10.7554/eLife.53103

Share this article

https://doi.org/10.7554/eLife.53103

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Further reading

    1. Neuroscience

    Regulation of starvation-induced hyperactivity by insulin and glucagon signaling in adult Drosophila

    Yue Yu, Rui Huang ... Liming Wang
    Research Article Updated

    Starvation induces sustained increase in locomotion, which facilitates food localization and acquisition and hence composes an important aspect of food-seeking behavior. We investigated how nutritional states modulated starvation-induced hyperactivity in adult Drosophila. The receptor of the adipokinetic hormone (AKHR), the insect analog of glucagon, was required for starvation-induced hyperactivity. AKHR was expressed in a small group of octopaminergic neurons in the brain. Silencing AKHR+ neurons and blocking octopamine signaling in these neurons eliminated starvation-induced hyperactivity, whereas activation of these neurons accelerated the onset of hyperactivity upon starvation. Neither AKHR nor AKHR+ neurons were involved in increased food consumption upon starvation, suggesting that starvation-induced hyperactivity and food consumption are independently regulated. Single cell analysis of AKHR+ neurons identified the co-expression of Drosophila insulin-like receptor (dInR), which imposed suppressive effect on starvation-induced hyperactivity. Therefore, insulin and glucagon signaling exert opposite effects on starvation-induced hyperactivity via a common neural target in Drosophila.