High-fat diet enhances starvation-induced hyperactivity via sensitizing hunger-sensing neurons in Drosophila
- Chongqing University, China
- Shenzhen Bay Laboratory, China
- Institute of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, China
- Zhejiang University, China
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.
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High-fat diet enhances food-seeking behavior via sensitizing hunger-sensing neurons in Drosophila IINCBI Gene Expression Omnibus, GSE129602.
Article and author information
Author details
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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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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