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Title: Transcriptional signatures of the small intestinal mucosa in response to ethanol in transgenic mice rich in endogenous n3 fatty acids.

Authors: 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

Published In Sci Rep, (2020 11 16)

Abstract: 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.

PubMed ID: 33199802 Exiting the NIEHS site

MeSH Terms: Animals; Cadherins/physiology*; Dietary Fats/administration & dosage*; Ethanol/pharmacology*; Fatty Acids, Omega-3/metabolism*; Gene Expression Profiling*; Gene Expression Regulation/drug effects*; Intestinal Mucosa/drug effects; Intestinal Mucosa/growth & development; Intestinal Mucosa/metabolism*; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic

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