NAD Supplement Alleviates Intestinal Barrier Injury Induced by Ethanol Via Protecting Epithelial Mitochondrial Function
Background: The epithelial tight junction is an important intestinal barrier whose disruption can lead to the release of harmful intestinal substances into the circulation and cause damage to systemic injury. The maintenance of intestinal epithelial tight junctions is closely related to energy homeo...
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MDPI AG
2022-12-01
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| Series: | Nutrients |
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| Online Access: | https://www.mdpi.com/2072-6643/15/1/174 |
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| author | Wenli Li Yujia Zhou Nengzhi Pang Qianrong Hu Qiuyan Li Yan Sun Yijie Ding Yingying Gu Ying Xiao Mengqi Gao Sixi Ma Jie Pan Evandro Fei Fang Zhenfeng Zhang Lili Yang |
| author_facet | Wenli Li Yujia Zhou Nengzhi Pang Qianrong Hu Qiuyan Li Yan Sun Yijie Ding Yingying Gu Ying Xiao Mengqi Gao Sixi Ma Jie Pan Evandro Fei Fang Zhenfeng Zhang Lili Yang |
| author_sort | Wenli Li |
| collection | DOAJ |
| description | Background: The epithelial tight junction is an important intestinal barrier whose disruption can lead to the release of harmful intestinal substances into the circulation and cause damage to systemic injury. The maintenance of intestinal epithelial tight junctions is closely related to energy homeostasis and mitochondrial function. Nicotinamide riboside (NR) is a NAD booster that can enhance mitochondrial biogenesis in liver. However, whether NR can prevent ethanol-induced intestinal barrier dysfunction and the underlying mechanisms remain unclear. Methods: We applied the mouse NIAAA model (chronic plus binge ethanol feeding) and Caco-2 cells to explore the effects of NR on ethanol-induced intestinal barrier dysfunction and the underlying mechanisms. NAD homeostasis and mitochondrial function were measured. In addition, knockdown of SirT1 in Caco-2 cells was further applied to explore the role of SirT1 in the protection of NR. Results: We found that ethanol increased intestinal permeability, increased the release of LPS into the circulation and destroyed the intestinal epithelial barrier structure in mice. NR supplementation attenuated intestinal barrier injury. Both in vivo and in vitro experiments showed that NR attenuated ethanol-induced decreased intestinal tight junction protein expressions and maintained NAD homeostasis. In addition, NR supplementation activated SirT1 activity and increased deacetylation of PGC-1α, and reversed ethanol-induced mitochondrial dysfunction and mitochondrial biogenesis. These effects were diminished with the knockdown of SirT1 in Caco-2 cells. Conclusion: Boosting NAD by NR alleviates ethanol-induced intestinal epithelial barrier damage via protecting mitochondrial function in a SirT1-dependent manner. |
| first_indexed | 2024-03-09T09:44:06Z |
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| id | doaj.art-d476fdcf982f481c9ccbef61f27f62ab |
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| language | English |
| last_indexed | 2024-03-09T09:44:06Z |
| publishDate | 2022-12-01 |
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| series | Nutrients |
| spelling | doaj.art-d476fdcf982f481c9ccbef61f27f62ab2023-12-02T00:46:17ZengMDPI AGNutrients2072-66432022-12-0115117410.3390/nu15010174NAD Supplement Alleviates Intestinal Barrier Injury Induced by Ethanol Via Protecting Epithelial Mitochondrial FunctionWenli Li0Yujia Zhou1Nengzhi Pang2Qianrong Hu3Qiuyan Li4Yan Sun5Yijie Ding6Yingying Gu7Ying Xiao8Mengqi Gao9Sixi Ma10Jie Pan11Evandro Fei Fang12Zhenfeng Zhang13Lili Yang14Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University, No. 74 Zhongshan Road 2, Yuexiu District, Guangzhou 510080, ChinaGuangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University, No. 74 Zhongshan Road 2, Yuexiu District, Guangzhou 510080, ChinaGuangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University, No. 74 Zhongshan Road 2, Yuexiu District, Guangzhou 510080, ChinaGuangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University, No. 74 Zhongshan Road 2, Yuexiu District, Guangzhou 510080, ChinaGuangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University, No. 74 Zhongshan Road 2, Yuexiu District, Guangzhou 510080, ChinaGuangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University, No. 74 Zhongshan Road 2, Yuexiu District, Guangzhou 510080, ChinaGuangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University, No. 74 Zhongshan Road 2, Yuexiu District, Guangzhou 510080, ChinaGuangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University, No. 74 Zhongshan Road 2, Yuexiu District, Guangzhou 510080, ChinaGuangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University, No. 74 Zhongshan Road 2, Yuexiu District, Guangzhou 510080, ChinaGuangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University, No. 74 Zhongshan Road 2, Yuexiu District, Guangzhou 510080, ChinaGuangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University, No. 74 Zhongshan Road 2, Yuexiu District, Guangzhou 510080, ChinaGuangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University, No. 74 Zhongshan Road 2, Yuexiu District, Guangzhou 510080, ChinaDepartment of Clinical Molecular Biology, University of Oslo and Akershus University Hospital, 1478 Lørenskog, NorwayRadiology Center, Translational Medicine Center, Guangzhou Key Laboratory for Research and Development of Nano-Biomedical Technology for Diagnosis and Therapy, Guangdong Provincial Education Department, Key Laboratory of Nano-Immunoregulation Tumour Microenvironment, Central Laboratory, the Second Affiliated Hospital, Guangzhou Medical University, Guangzhou 510260, ChinaGuangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University, No. 74 Zhongshan Road 2, Yuexiu District, Guangzhou 510080, ChinaBackground: The epithelial tight junction is an important intestinal barrier whose disruption can lead to the release of harmful intestinal substances into the circulation and cause damage to systemic injury. The maintenance of intestinal epithelial tight junctions is closely related to energy homeostasis and mitochondrial function. Nicotinamide riboside (NR) is a NAD booster that can enhance mitochondrial biogenesis in liver. However, whether NR can prevent ethanol-induced intestinal barrier dysfunction and the underlying mechanisms remain unclear. Methods: We applied the mouse NIAAA model (chronic plus binge ethanol feeding) and Caco-2 cells to explore the effects of NR on ethanol-induced intestinal barrier dysfunction and the underlying mechanisms. NAD homeostasis and mitochondrial function were measured. In addition, knockdown of SirT1 in Caco-2 cells was further applied to explore the role of SirT1 in the protection of NR. Results: We found that ethanol increased intestinal permeability, increased the release of LPS into the circulation and destroyed the intestinal epithelial barrier structure in mice. NR supplementation attenuated intestinal barrier injury. Both in vivo and in vitro experiments showed that NR attenuated ethanol-induced decreased intestinal tight junction protein expressions and maintained NAD homeostasis. In addition, NR supplementation activated SirT1 activity and increased deacetylation of PGC-1α, and reversed ethanol-induced mitochondrial dysfunction and mitochondrial biogenesis. These effects were diminished with the knockdown of SirT1 in Caco-2 cells. Conclusion: Boosting NAD by NR alleviates ethanol-induced intestinal epithelial barrier damage via protecting mitochondrial function in a SirT1-dependent manner.https://www.mdpi.com/2072-6643/15/1/174nicotinamide adenine dinucleotide (NAD)nicotinamide riboside (NR)intestinal barriertight junctions (TJs)SirT1mitochondrial function |
| spellingShingle | Wenli Li Yujia Zhou Nengzhi Pang Qianrong Hu Qiuyan Li Yan Sun Yijie Ding Yingying Gu Ying Xiao Mengqi Gao Sixi Ma Jie Pan Evandro Fei Fang Zhenfeng Zhang Lili Yang NAD Supplement Alleviates Intestinal Barrier Injury Induced by Ethanol Via Protecting Epithelial Mitochondrial Function Nutrients nicotinamide adenine dinucleotide (NAD) nicotinamide riboside (NR) intestinal barrier tight junctions (TJs) SirT1 mitochondrial function |
| title | NAD Supplement Alleviates Intestinal Barrier Injury Induced by Ethanol Via Protecting Epithelial Mitochondrial Function |
| title_full | NAD Supplement Alleviates Intestinal Barrier Injury Induced by Ethanol Via Protecting Epithelial Mitochondrial Function |
| title_fullStr | NAD Supplement Alleviates Intestinal Barrier Injury Induced by Ethanol Via Protecting Epithelial Mitochondrial Function |
| title_full_unstemmed | NAD Supplement Alleviates Intestinal Barrier Injury Induced by Ethanol Via Protecting Epithelial Mitochondrial Function |
| title_short | NAD Supplement Alleviates Intestinal Barrier Injury Induced by Ethanol Via Protecting Epithelial Mitochondrial Function |
| title_sort | nad supplement alleviates intestinal barrier injury induced by ethanol via protecting epithelial mitochondrial function |
| topic | nicotinamide adenine dinucleotide (NAD) nicotinamide riboside (NR) intestinal barrier tight junctions (TJs) SirT1 mitochondrial function |
| url | https://www.mdpi.com/2072-6643/15/1/174 |
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