A High-Fat Diet Activates the BAs-FXR Axis and Triggers Cancer-Associated Fibroblast Properties in the ColonSummary
Background & Aims: Dietary signals are known to modulate stemness and tumorigenicity of intestinal progenitors; however, the impact of a high-fat diet (HFD) on the intestinal stem cell (ISC) niche and its association with colorectal cancer remains unclear. Thus, we aimed to investigate how a...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-01-01
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| Series: | Cellular and Molecular Gastroenterology and Hepatology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352345X21002654 |
| _version_ | 1818329801986932736 |
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| author | Tae-Young Kim Seungil Kim Yeji Kim Yong-Soo Lee Sohyeon Lee Su-Hyun Lee Mi-Na Kweon |
| author_facet | Tae-Young Kim Seungil Kim Yeji Kim Yong-Soo Lee Sohyeon Lee Su-Hyun Lee Mi-Na Kweon |
| author_sort | Tae-Young Kim |
| collection | DOAJ |
| description | Background & Aims: Dietary signals are known to modulate stemness and tumorigenicity of intestinal progenitors; however, the impact of a high-fat diet (HFD) on the intestinal stem cell (ISC) niche and its association with colorectal cancer remains unclear. Thus, we aimed to investigate how a HFD affects the ISC niche and its regulatory factors. Methods: Mice were fed a purified diet (PD) or HFD for 2 months. The expression levels of ISC-related markers, ISC-supportive signals, and Wnt2b were assessed with real-time quantitative polymerase chain reaction, in situ hybridization, and immunofluorescence staining. RNA sequencing and metabolic function were analyzed in mesenchymal stromal cells (MSCs) from PD- and HFD-fed mice. Fecal microbiota were analyzed by 16s rRNA sequencing. Bile salt hydrolase activity and bile acid (BA) levels were measured. Results: We found that expression of CD44 and Wnt signal-related genes was higher in the colonic crypts of HFD-fed mice than in those fed a PD. Within the ISC niche, MSCs were expanded and secreted predominant levels of Wnt2b in the colon of HFD-fed mice. Of note, increased energy metabolism and cancer-associated fibroblast (CAF)-like properties were found in the colonic MSCs of HFD-fed mice. Moreover, colonic MSCs from HFD-fed mice promoted the growth of tumorigenic properties and accelerated the expression of cancer stem cell (CSC)-related markers in colon organoids. In particular, production of primary and secondary BAs was increased through the expansion of bile salt hydrolase-encoding bacteria in HFD-fed mice. Most importantly, BAs-FXR interaction stimulated Wnt2b production in colonic CAF-like MSCs. Conclusions: HFD-induced colonic CAF-like MSCs play an indispensable role in balancing the properties of CSCs through activation of the BAs-FXR axis. |
| first_indexed | 2024-12-13T12:53:50Z |
| format | Article |
| id | doaj.art-17a0212ccc5a4503a8d02af3da7b4005 |
| institution | Directory Open Access Journal |
| issn | 2352-345X |
| language | English |
| last_indexed | 2024-12-13T12:53:50Z |
| publishDate | 2022-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cellular and Molecular Gastroenterology and Hepatology |
| spelling | doaj.art-17a0212ccc5a4503a8d02af3da7b40052022-12-21T23:45:15ZengElsevierCellular and Molecular Gastroenterology and Hepatology2352-345X2022-01-0113411411159A High-Fat Diet Activates the BAs-FXR Axis and Triggers Cancer-Associated Fibroblast Properties in the ColonSummaryTae-Young Kim0Seungil Kim1Yeji Kim2Yong-Soo Lee3Sohyeon Lee4Su-Hyun Lee5Mi-Na Kweon6Mucosal Immunology Laboratory, Department of Convergence Medicine, University of Ulsan College of Medicine/Asan Medical Center, SeoulMucosal Immunology Laboratory, Department of Convergence Medicine, University of Ulsan College of Medicine/Asan Medical Center, Seoul; Digestive Diseases Research Center, University of Ulsan College of Medicine, Seoul, Republic of KoreaMucosal Immunology Laboratory, Department of Convergence Medicine, University of Ulsan College of Medicine/Asan Medical Center, SeoulMucosal Immunology Laboratory, Department of Convergence Medicine, University of Ulsan College of Medicine/Asan Medical Center, SeoulMucosal Immunology Laboratory, Department of Convergence Medicine, University of Ulsan College of Medicine/Asan Medical Center, SeoulMucosal Immunology Laboratory, Department of Convergence Medicine, University of Ulsan College of Medicine/Asan Medical Center, SeoulMucosal Immunology Laboratory, Department of Convergence Medicine, University of Ulsan College of Medicine/Asan Medical Center, Seoul; Digestive Diseases Research Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; Correspondence Address correspondence to: Mi-Na Kweon, PhD, Asan Medical Center, Department of Convergence Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Republic of Korea. fax: +82 2-3010-4234.Background & Aims: Dietary signals are known to modulate stemness and tumorigenicity of intestinal progenitors; however, the impact of a high-fat diet (HFD) on the intestinal stem cell (ISC) niche and its association with colorectal cancer remains unclear. Thus, we aimed to investigate how a HFD affects the ISC niche and its regulatory factors. Methods: Mice were fed a purified diet (PD) or HFD for 2 months. The expression levels of ISC-related markers, ISC-supportive signals, and Wnt2b were assessed with real-time quantitative polymerase chain reaction, in situ hybridization, and immunofluorescence staining. RNA sequencing and metabolic function were analyzed in mesenchymal stromal cells (MSCs) from PD- and HFD-fed mice. Fecal microbiota were analyzed by 16s rRNA sequencing. Bile salt hydrolase activity and bile acid (BA) levels were measured. Results: We found that expression of CD44 and Wnt signal-related genes was higher in the colonic crypts of HFD-fed mice than in those fed a PD. Within the ISC niche, MSCs were expanded and secreted predominant levels of Wnt2b in the colon of HFD-fed mice. Of note, increased energy metabolism and cancer-associated fibroblast (CAF)-like properties were found in the colonic MSCs of HFD-fed mice. Moreover, colonic MSCs from HFD-fed mice promoted the growth of tumorigenic properties and accelerated the expression of cancer stem cell (CSC)-related markers in colon organoids. In particular, production of primary and secondary BAs was increased through the expansion of bile salt hydrolase-encoding bacteria in HFD-fed mice. Most importantly, BAs-FXR interaction stimulated Wnt2b production in colonic CAF-like MSCs. Conclusions: HFD-induced colonic CAF-like MSCs play an indispensable role in balancing the properties of CSCs through activation of the BAs-FXR axis.http://www.sciencedirect.com/science/article/pii/S2352345X21002654Cancer Stem CellsGut MicrobiomeMesenchymal Stromal CellsWnt2b |
| spellingShingle | Tae-Young Kim Seungil Kim Yeji Kim Yong-Soo Lee Sohyeon Lee Su-Hyun Lee Mi-Na Kweon A High-Fat Diet Activates the BAs-FXR Axis and Triggers Cancer-Associated Fibroblast Properties in the ColonSummary Cellular and Molecular Gastroenterology and Hepatology Cancer Stem Cells Gut Microbiome Mesenchymal Stromal Cells Wnt2b |
| title | A High-Fat Diet Activates the BAs-FXR Axis and Triggers Cancer-Associated Fibroblast Properties in the ColonSummary |
| title_full | A High-Fat Diet Activates the BAs-FXR Axis and Triggers Cancer-Associated Fibroblast Properties in the ColonSummary |
| title_fullStr | A High-Fat Diet Activates the BAs-FXR Axis and Triggers Cancer-Associated Fibroblast Properties in the ColonSummary |
| title_full_unstemmed | A High-Fat Diet Activates the BAs-FXR Axis and Triggers Cancer-Associated Fibroblast Properties in the ColonSummary |
| title_short | A High-Fat Diet Activates the BAs-FXR Axis and Triggers Cancer-Associated Fibroblast Properties in the ColonSummary |
| title_sort | high fat diet activates the bas fxr axis and triggers cancer associated fibroblast properties in the colonsummary |
| topic | Cancer Stem Cells Gut Microbiome Mesenchymal Stromal Cells Wnt2b |
| url | http://www.sciencedirect.com/science/article/pii/S2352345X21002654 |
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