Exposure to high-sugar diet induces transgenerational changes in sweet sensitivity and feeding behavior via H3K27me3 reprogramming
- Zhejiang University, China
- Xiangya Hospital Central South University, China
- Chongqing University, China
- Shenzhen Bay Laboratory, China
Abstract
Human health is facing a host of new threats linked to unbalanced diets, including high sugar diet (HSD), which contributes to the development of both metabolic and behavioral disorders. Studies have shown that diet-induced metabolic dysfunctions can be transmitted to multiple generations of offspring and exert long-lasting health burden. Meanwhile, whether and how diet-induced behavioral abnormalities can be transmitted to the offspring remains largely unclear. Here, we showed that ancestral HSD exposure suppressed sweet sensitivity and feeding behavior in the offspring in Drosophila. These behavioral deficits were transmitted through the maternal germline and companied by the enhancement of H3K27me3 modifications. PCL-PRC2 complex, a major driver of H3K27 trimethylation, was upregulated by ancestral HSD exposure, and disrupting its activity eliminated the transgenerational inheritance of sweet sensitivity and feeding behavior deficits. Elevated H3K27me3 inhibited the expression of a transcriptional factor Cad and suppressed sweet sensitivity of the sweet-sensing gustatory neurons, reshaping the sweet perception and feeding behavior of the offspring. Taken together, we uncovered a novel molecular mechanism underlying behavioral abnormalities spanning multiple generations of offspring upon ancestral HSD exposure, which would contribute to the further understanding of long-term health risk of unbalanced diet.
Data availability
Sequencing data have been deposited in GEO under accession codes GSE216075 and GSE215756.All data generated or analysed during this study are included in the manuscript and supporting file; Source Data files have been provided for all figures and supplementary figures.
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Histone methylation mediates transgenerational modulations of sweet perception by high sugar diet [ChIP-Seq]NCBI Gene Expression Omnibus, GSE216075.
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Histone methylation mediates transgenerational modulations of sweet perception by high sugar dietNCBI Gene Expression Omnibus, GSE215756.
Article and author information
Author details
Funding
National Key Research and Development Program of China (2019YFA0802400)
- Liming Wang
National Key Research and Development Program of China (2019YFA0801900)
- Liming Wang
National Natural Science Foundation of China (32071006)
- Liming Wang
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2023, Yang 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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Exposure to high-sugar diet induces transgenerational changes in sweet sensitivity and feeding behavior via H3K27me3 reprogramming
eLife 12:e85365.
https://doi.org/10.7554/eLife.85365
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