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Gut taste receptor type 1 member 3 is an intrinsic regulator of Western diet-induced intestinal inflammation
DC Field | Value | Language |
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dc.contributor.author | Shon, Woo-Jeong | - |
dc.contributor.author | Song, Jae Won | - |
dc.contributor.author | Oh, Seung Hoon | - |
dc.contributor.author | Lee, Keon-Hee | - |
dc.contributor.author | Seong, Hobin | - |
dc.contributor.author | You, Hyun Ju | - |
dc.contributor.author | Seong, Je Kyung | - |
dc.contributor.author | Shin, Dong-Mi | - |
dc.date.accessioned | 2023-05-16T02:23:22Z | - |
dc.date.available | 2023-05-16T11:24:03Z | - |
dc.date.issued | 2023-04-28 | - |
dc.identifier.citation | BMC Medicine, 21(1):165 | ko_KR |
dc.identifier.issn | 1741-7015 | - |
dc.identifier.uri | https://hdl.handle.net/10371/192422 | - |
dc.description.abstract | Background
Long-term intake of a Western diet (WD), characterized by a high-fat content and sugary drinks, is hypothesized to contribute to the development of inflammatory bowel disease (IBD). Despite the identified clinical association, the molecular mechanisms by which dietary changes contribute to IBD development remain unknown. Therefore, we examined the influence of long-term intake of a WD on intestinal inflammation and the mechanisms by which WD intake affects IBD development. Methods Mice fed normal diet or WD for 10weeks, and bowel inflammation was evaluated through pathohistological and infiltrated inflammatory cell assessments. To understand the role of intestinal taste receptor type 1 member 3 (TAS1R3) in WD-induced intestinal inflammation, cultured enteroendocrine cells harboring TAS1R3, subjected to RNA interference or antagonist treatment, and Tas1r3-deficient mice were used. RNA-sequencing, flow cytometry, 16S metagenomic sequencing, and bioinformatics analyses were performed to examine the involved mechanisms. To demonstrate their clinical relevance, intestinal biopsies from patients with IBD and mice with dextran sulfate sodium-induced colitis were analyzed. Results Our study revealed for the first time that intestinal TAS1R3 is a critical mediator of WD-induced intestinal inflammation. WD-fed mice showed marked TAS1R3 overexpression with hallmarks of serious bowel inflammation. Conversely, mice lacking TAS1R3 failed to exhibit inflammatory responses to WD. Mechanistically, intestinal transcriptome analysis revealed that Tas1r3 deficiency suppressed mTOR signaling, significantly increasing the expression of PPARγ (a major mucosal defense enhancer) and upregulating the expression of PPARγ target-gene (tight junction protein and antimicrobial peptide). The gut microbiota of Tas1r3-deficient mice showed expansion of butyrate-producing Clostridia. Moreover, an increased expression of host PPARγ-signaling pathway proteins was positively correlated with butyrate-producing microbes, suggesting that intestinal TAS1R3 regulates the relationship between host metabolism and gut microflora in response to dietary factors. In cultured intestinal cells, regulation of the TAS1R3–mTOR–PPARγ axis was critical for triggering an inflammatory response via proinflammatory cytokine production and secretion. Abnormal regulation of the axis was observed in patients with IBD. Conclusions Our findings suggest that the TAS1R3–mTOR–PPARγ axis in the gut links Western diet consumption with intestinal inflammation and is a potential therapeutic target for IBD. | ko_KR |
dc.description.sponsorship | This work was supported by the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education (Grant NRF-2021R1A2C3010280), and the Korea Mouse Phenotyping Project through the National Research Foundation of Korea funded by the Ministry of Science and ICT (Grant NRF-2013M3A9D5072550). The funding sources had no role in the design of the study, in the collection, analysis, and interpretation of data, or in the writing of the manuscript | ko_KR |
dc.language.iso | en | ko_KR |
dc.publisher | BMC | ko_KR |
dc.subject | Butyrate-producing microbes | - |
dc.subject | Clostridia | - |
dc.subject | Gut-taste receptor | - |
dc.subject | Inflammatory bowel disease | - |
dc.subject | Intestinal PPAR-γ | - |
dc.subject | mTOR signaling | - |
dc.subject | Taste receptor type 1 member 3 | - |
dc.subject | Western diet | - |
dc.title | Gut taste receptor type 1 member 3 is an intrinsic regulator of Western diet-induced intestinal inflammation | ko_KR |
dc.type | Article | ko_KR |
dc.identifier.doi | 10.1186/s12916-023-02848-0 | ko_KR |
dc.citation.journaltitle | BMC Medicine | ko_KR |
dc.language.rfc3066 | en | - |
dc.rights.holder | The Author(s) | - |
dc.date.updated | 2023-04-30T03:12:47Z | - |
dc.citation.number | 165 | ko_KR |
dc.citation.volume | 21 | ko_KR |
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