Cargando…
Transcriptional signatures of the small intestinal mucosa in response to ethanol in transgenic mice rich in endogenous n3 fatty acids
The intestine interacts with many factors, including dietary components and ethanol (EtOH), which can impact intestinal health. Previous studies showed that different types of dietary fats can modulate EtOH-induced changes in the intestine; however, mechanisms underlying these effects are not comple...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7670449/ https://www.ncbi.nlm.nih.gov/pubmed/33199802 http://dx.doi.org/10.1038/s41598-020-76959-6 |
_version_ | 1783610740636123136 |
---|---|
author | Hardesty, Josiah E. Warner, Jeffrey B. Song, Ying L. Rouchka, Eric C. Chen, Chih-Yu Kang, Jing X. McClain, Craig J. Warner, Dennis R. Kirpich, Irina A. |
author_facet | Hardesty, Josiah E. Warner, Jeffrey B. Song, Ying L. Rouchka, Eric C. Chen, Chih-Yu Kang, Jing X. McClain, Craig J. Warner, Dennis R. Kirpich, Irina A. |
author_sort | Hardesty, Josiah E. |
collection | PubMed |
description | The intestine interacts with many factors, including dietary components and ethanol (EtOH), which can impact intestinal health. Previous studies showed that different types of dietary fats can modulate EtOH-induced changes in the intestine; however, mechanisms underlying these effects are not completely understood. Here, we examined intestinal transcriptional responses to EtOH in WT and transgenic fat-1 mice (which endogenously convert n6 to n3 polyunsaturated fatty acids [PUFAs]) to identify novel genes and pathways involved in EtOH-associated gut pathology and discern the impact of n3 PUFA enrichment. WT and fat-1 mice were chronically fed EtOH, and ileum RNA-seq and bioinformatic analyses were performed. EtOH consumption led to a marked down-regulation of genes encoding digestive and xenobiotic-metabolizing enzymes, and transcription factors involved in developmental processes and tissue regeneration. Compared to WT, fat-1 mice exhibited a markedly plastic transcriptome response to EtOH. Cell death, inflammation, and tuft cell markers were downregulated in fat-1 mice in response to EtOH, while defense responses and PPAR signaling were upregulated. This transcriptional reprogramming may contribute to the beneficial effects of n3 PUFAs on EtOH-induced intestinal pathology. In summary, our study provides a reference dataset of the intestinal mucosa transcriptional responses to chronic EtOH exposure for future hypothesis-driven mechanistic studies. |
format | Online Article Text |
id | pubmed-7670449 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-76704492020-11-18 Transcriptional signatures of the small intestinal mucosa in response to ethanol in transgenic mice rich in endogenous n3 fatty acids Hardesty, Josiah E. Warner, Jeffrey B. Song, Ying L. Rouchka, Eric C. Chen, Chih-Yu Kang, Jing X. McClain, Craig J. Warner, Dennis R. Kirpich, Irina A. Sci Rep Article The intestine interacts with many factors, including dietary components and ethanol (EtOH), which can impact intestinal health. Previous studies showed that different types of dietary fats can modulate EtOH-induced changes in the intestine; however, mechanisms underlying these effects are not completely understood. Here, we examined intestinal transcriptional responses to EtOH in WT and transgenic fat-1 mice (which endogenously convert n6 to n3 polyunsaturated fatty acids [PUFAs]) to identify novel genes and pathways involved in EtOH-associated gut pathology and discern the impact of n3 PUFA enrichment. WT and fat-1 mice were chronically fed EtOH, and ileum RNA-seq and bioinformatic analyses were performed. EtOH consumption led to a marked down-regulation of genes encoding digestive and xenobiotic-metabolizing enzymes, and transcription factors involved in developmental processes and tissue regeneration. Compared to WT, fat-1 mice exhibited a markedly plastic transcriptome response to EtOH. Cell death, inflammation, and tuft cell markers were downregulated in fat-1 mice in response to EtOH, while defense responses and PPAR signaling were upregulated. This transcriptional reprogramming may contribute to the beneficial effects of n3 PUFAs on EtOH-induced intestinal pathology. In summary, our study provides a reference dataset of the intestinal mucosa transcriptional responses to chronic EtOH exposure for future hypothesis-driven mechanistic studies. Nature Publishing Group UK 2020-11-16 /pmc/articles/PMC7670449/ /pubmed/33199802 http://dx.doi.org/10.1038/s41598-020-76959-6 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Hardesty, Josiah E. Warner, Jeffrey B. Song, Ying L. Rouchka, Eric C. Chen, Chih-Yu Kang, Jing X. McClain, Craig J. Warner, Dennis R. Kirpich, Irina A. Transcriptional signatures of the small intestinal mucosa in response to ethanol in transgenic mice rich in endogenous n3 fatty acids |
title | Transcriptional signatures of the small intestinal mucosa in response to ethanol in transgenic mice rich in endogenous n3 fatty acids |
title_full | Transcriptional signatures of the small intestinal mucosa in response to ethanol in transgenic mice rich in endogenous n3 fatty acids |
title_fullStr | Transcriptional signatures of the small intestinal mucosa in response to ethanol in transgenic mice rich in endogenous n3 fatty acids |
title_full_unstemmed | Transcriptional signatures of the small intestinal mucosa in response to ethanol in transgenic mice rich in endogenous n3 fatty acids |
title_short | Transcriptional signatures of the small intestinal mucosa in response to ethanol in transgenic mice rich in endogenous n3 fatty acids |
title_sort | transcriptional signatures of the small intestinal mucosa in response to ethanol in transgenic mice rich in endogenous n3 fatty acids |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7670449/ https://www.ncbi.nlm.nih.gov/pubmed/33199802 http://dx.doi.org/10.1038/s41598-020-76959-6 |
work_keys_str_mv | AT hardestyjosiahe transcriptionalsignaturesofthesmallintestinalmucosainresponsetoethanolintransgenicmicerichinendogenousn3fattyacids AT warnerjeffreyb transcriptionalsignaturesofthesmallintestinalmucosainresponsetoethanolintransgenicmicerichinendogenousn3fattyacids AT songyingl transcriptionalsignaturesofthesmallintestinalmucosainresponsetoethanolintransgenicmicerichinendogenousn3fattyacids AT rouchkaericc transcriptionalsignaturesofthesmallintestinalmucosainresponsetoethanolintransgenicmicerichinendogenousn3fattyacids AT chenchihyu transcriptionalsignaturesofthesmallintestinalmucosainresponsetoethanolintransgenicmicerichinendogenousn3fattyacids AT kangjingx transcriptionalsignaturesofthesmallintestinalmucosainresponsetoethanolintransgenicmicerichinendogenousn3fattyacids AT mcclaincraigj transcriptionalsignaturesofthesmallintestinalmucosainresponsetoethanolintransgenicmicerichinendogenousn3fattyacids AT warnerdennisr transcriptionalsignaturesofthesmallintestinalmucosainresponsetoethanolintransgenicmicerichinendogenousn3fattyacids AT kirpichirinaa transcriptionalsignaturesofthesmallintestinalmucosainresponsetoethanolintransgenicmicerichinendogenousn3fattyacids |