Page 33 - Read Online

Qu et al. J Transl Genet Genom 2023;7:3-16 Journal of Translational
DOI: 10.20517/jtgg.2022.16
Genetics and Genomics

Original Article Open Access

Epigenetic effects of high-fat diet on intestinal
tumorigenesis in C57BL/6J-Apc Min/+ mice

1
2
1
2
2
1
Dan C. Qu , Devin Neu , Zain Q. Khawaja , Ruoyu Wang , Cynthia F. Bartels , Katreya Lovrenert , Ernest R.
3
1
2,4
Chan , Anne E. Hill-Baskin , Peter C. Scacheri , Nathan A. Berger 1,4
1
Center for Science, Health and Society, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
2
Department of Genetics and Genome Sciences, Case Western Reserve University School of Medicine, Cleveland, OH 44106,
USA.
3
Cleveland Institute for Computational Biology, Case Western Reserve University, Cleveland, OH 44106, USA.
4
Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA.
Correspondence to: Dr. Nathan A. Berger, Center for Science, Health and Society, Case Western Reserve University School of
Medicine, 10900 Euclid Avenue, Cleveland, OH 44106, USA. E-mail: nab@case.edu
How to cite this article: Qu DC, Neu D, Khawaja ZQ, Wang R, Bartels CF, Lovrenert K, Chan ER, Hill-Baskin AE, Scacheri PC,
Berger NA. Epigenetic effects of high-fat diet on intestinal tumorigenesis in C57BL/6J-Apc Min/+ mice. J Transl Genet Genom
2023;7:3-16. https://dx.doi.org/10.20517/jtgg.2022.16
Received: 1 Aug 2022 First Decision: 26 Sep 2022 Revised: 3 Jan 2023 Accepted: 20 Jan 2023 Published: 31 Jan 2023
Academic Editor: Bridget Bax Copy Editor: Fangling Lan Production Editor: Fangling Lan
Abstract
Aim: Obesity and obesogenic diets might partly accelerate cancer development through epigenetic mechanisms.
To determine these early effects, we investigated the impact of three days of a high-fat diet on epigenomic and
transcriptomic changes in Apc Min /+ murine intestinal epithelia.

Method: ChIP-Seq and RNA-Seq were performed on small intestinal epithelia of WT and Apc Min /+ male mice fed
high-fat diet (HFD) or low-fat diet (LFD) for three days to identify genomic regions associated with differential
H3K27ac levels as a marker of variant enhancer loci (VELs) as well as differentially expressed genes (DEGs).

Results: Regarding epigenetic and transcriptomic changes, diet type (LFD vs. HFD) showed a significant impact,
and genotype (WT vs. Apc Min/+ ) showed a small impact. Compared to LFD, HFD resulted in 1306 gained VELs,
230 lost VELs, 133 upregulated genes, and 127 downregulated genes in WT mice, with 1056 gained VELs, 371 lost
VELs, 222 upregulated genes, and 182 downregulated genes in Apc Min/+ mice. Compared to the WT genotype, the
Apc Min/+ genotype resulted in zero changed VELs for either diet type group, 21 DEGs for LFD, and 48 DEGs for
HFD. Most gained VELs, and upregulated genes were associated with lipid metabolic processes. Gained VELs were

© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing,
adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as
long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and
indicate if changes were made.

www.jtggjournal.com