Trimethylamine N-Oxide Exacerbates Renal Inflammation and Fibrosis in Rats With Diabetic Kidney Disease
The gut microbiota plays a pivotal role in the onset and development of diabetes and its complications. Trimethylamine N-oxide (TMAO), a gut microbiota-dependent metabolite of certain nutrients, is associated with type 2 diabetes and its complications. Diabetic kidney disease (DKD) is one of the mos...
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Frontiers Media S.A.
2021-06-01
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| Series: | Frontiers in Physiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphys.2021.682482/full |
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| author | Qing Fang Qing Fang Qing Fang Qing Fang Qing Fang Binjie Zheng Binjie Zheng Binjie Zheng Binjie Zheng Binjie Zheng Na Liu Na Liu Na Liu Na Liu Na Liu Jinfeng Liu Jinfeng Liu Jinfeng Liu Jinfeng Liu Jinfeng Liu Wenhui Liu Wenhui Liu Wenhui Liu Wenhui Liu Wenhui Liu Xinyi Huang Xinyi Huang Xinyi Huang Xinyi Huang Xinyi Huang Xiangchang Zeng Xiangchang Zeng Xiangchang Zeng Xiangchang Zeng Xiangchang Zeng Lulu Chen Zhenyu Li Dongsheng Ouyang Dongsheng Ouyang Dongsheng Ouyang Dongsheng Ouyang Dongsheng Ouyang |
| author_facet | Qing Fang Qing Fang Qing Fang Qing Fang Qing Fang Binjie Zheng Binjie Zheng Binjie Zheng Binjie Zheng Binjie Zheng Na Liu Na Liu Na Liu Na Liu Na Liu Jinfeng Liu Jinfeng Liu Jinfeng Liu Jinfeng Liu Jinfeng Liu Wenhui Liu Wenhui Liu Wenhui Liu Wenhui Liu Wenhui Liu Xinyi Huang Xinyi Huang Xinyi Huang Xinyi Huang Xinyi Huang Xiangchang Zeng Xiangchang Zeng Xiangchang Zeng Xiangchang Zeng Xiangchang Zeng Lulu Chen Zhenyu Li Dongsheng Ouyang Dongsheng Ouyang Dongsheng Ouyang Dongsheng Ouyang Dongsheng Ouyang |
| author_sort | Qing Fang |
| collection | DOAJ |
| description | The gut microbiota plays a pivotal role in the onset and development of diabetes and its complications. Trimethylamine N-oxide (TMAO), a gut microbiota-dependent metabolite of certain nutrients, is associated with type 2 diabetes and its complications. Diabetic kidney disease (DKD) is one of the most serious microvascular complications. However, whether TMAO accelerates the development of DKD remains unclear. We tested the hypothesis that TMAO accelerates the development of DKD. A high-fat diet/low-dose streptozotocin-induced diabetes rat model was established, with or without TMAO in the rats’ drinking water. Compared to the normal rats, the DKD rats showed significantly higher plasma TMAO levels at the end of the study. TMAO treatment not only exacerbated the kidney dysfunction of the DKD rats, but also renal fibrosis. Furthermore, TMAO treatment activated the nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome and resulted in the release of interleukin (IL)-1β and IL-18 to accelerate renal inflammation. These results suggested that TMAO aggravated renal inflammation and fibrosis in the DKD rats, which provides a new perspective to understand the pathogenesis of DKD and a potential novel target for preventing the progression of DKD. |
| first_indexed | 2024-12-19T19:56:37Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-12-19T19:56:37Z |
| publishDate | 2021-06-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Physiology |
| spelling | doaj.art-44ad8af0a4a041709634621b898a74492022-12-21T20:07:47ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2021-06-011210.3389/fphys.2021.682482682482Trimethylamine N-Oxide Exacerbates Renal Inflammation and Fibrosis in Rats With Diabetic Kidney DiseaseQing Fang0Qing Fang1Qing Fang2Qing Fang3Qing Fang4Binjie Zheng5Binjie Zheng6Binjie Zheng7Binjie Zheng8Binjie Zheng9Na Liu10Na Liu11Na Liu12Na Liu13Na Liu14Jinfeng Liu15Jinfeng Liu16Jinfeng Liu17Jinfeng Liu18Jinfeng Liu19Wenhui Liu20Wenhui Liu21Wenhui Liu22Wenhui Liu23Wenhui Liu24Xinyi Huang25Xinyi Huang26Xinyi Huang27Xinyi Huang28Xinyi Huang29Xiangchang Zeng30Xiangchang Zeng31Xiangchang Zeng32Xiangchang Zeng33Xiangchang Zeng34Lulu Chen35Zhenyu Li36Dongsheng Ouyang37Dongsheng Ouyang38Dongsheng Ouyang39Dongsheng Ouyang40Dongsheng Ouyang41Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, ChinaHunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology, Central South University, Changsha, ChinaEngineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, ChinaNational Clinical Research Center for Geriatric Disorders, Changsha, ChinaHunan Key Laboratory for Bioanalysis of Complex Matrix Samples, Changsha Duxact Biotech Co., Ltd., Changsha, ChinaDepartment of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, ChinaHunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology, Central South University, Changsha, ChinaEngineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, ChinaNational Clinical Research Center for Geriatric Disorders, Changsha, ChinaHunan Key Laboratory for Bioanalysis of Complex Matrix Samples, Changsha Duxact Biotech Co., Ltd., Changsha, ChinaDepartment of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, ChinaHunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology, Central South University, Changsha, ChinaEngineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, ChinaNational Clinical Research Center for Geriatric Disorders, Changsha, ChinaHunan Key Laboratory for Bioanalysis of Complex Matrix Samples, Changsha Duxact Biotech Co., Ltd., Changsha, ChinaDepartment of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, ChinaHunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology, Central South University, Changsha, ChinaEngineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, ChinaNational Clinical Research Center for Geriatric Disorders, Changsha, ChinaHunan Key Laboratory for Bioanalysis of Complex Matrix Samples, Changsha Duxact Biotech Co., Ltd., Changsha, ChinaDepartment of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, ChinaHunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology, Central South University, Changsha, ChinaEngineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, ChinaNational Clinical Research Center for Geriatric Disorders, Changsha, ChinaHunan Key Laboratory for Bioanalysis of Complex Matrix Samples, Changsha Duxact Biotech Co., Ltd., Changsha, ChinaDepartment of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, ChinaHunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology, Central South University, Changsha, ChinaEngineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, ChinaNational Clinical Research Center for Geriatric Disorders, Changsha, ChinaHunan Key Laboratory for Bioanalysis of Complex Matrix Samples, Changsha Duxact Biotech Co., Ltd., Changsha, ChinaDepartment of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, ChinaHunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology, Central South University, Changsha, ChinaEngineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, ChinaNational Clinical Research Center for Geriatric Disorders, Changsha, ChinaHunan Key Laboratory for Bioanalysis of Complex Matrix Samples, Changsha Duxact Biotech Co., Ltd., Changsha, ChinaHunan Key Laboratory for Bioanalysis of Complex Matrix Samples, Changsha Duxact Biotech Co., Ltd., Changsha, ChinaDepartment of Geriatric Medicine, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, ChinaHunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology, Central South University, Changsha, ChinaEngineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, ChinaNational Clinical Research Center for Geriatric Disorders, Changsha, ChinaHunan Key Laboratory for Bioanalysis of Complex Matrix Samples, Changsha Duxact Biotech Co., Ltd., Changsha, ChinaThe gut microbiota plays a pivotal role in the onset and development of diabetes and its complications. Trimethylamine N-oxide (TMAO), a gut microbiota-dependent metabolite of certain nutrients, is associated with type 2 diabetes and its complications. Diabetic kidney disease (DKD) is one of the most serious microvascular complications. However, whether TMAO accelerates the development of DKD remains unclear. We tested the hypothesis that TMAO accelerates the development of DKD. A high-fat diet/low-dose streptozotocin-induced diabetes rat model was established, with or without TMAO in the rats’ drinking water. Compared to the normal rats, the DKD rats showed significantly higher plasma TMAO levels at the end of the study. TMAO treatment not only exacerbated the kidney dysfunction of the DKD rats, but also renal fibrosis. Furthermore, TMAO treatment activated the nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome and resulted in the release of interleukin (IL)-1β and IL-18 to accelerate renal inflammation. These results suggested that TMAO aggravated renal inflammation and fibrosis in the DKD rats, which provides a new perspective to understand the pathogenesis of DKD and a potential novel target for preventing the progression of DKD.https://www.frontiersin.org/articles/10.3389/fphys.2021.682482/fulltrimethylamine N-oxidediabetic kidney diseaseinflammationNLRP3fibrosis |
| spellingShingle | Qing Fang Qing Fang Qing Fang Qing Fang Qing Fang Binjie Zheng Binjie Zheng Binjie Zheng Binjie Zheng Binjie Zheng Na Liu Na Liu Na Liu Na Liu Na Liu Jinfeng Liu Jinfeng Liu Jinfeng Liu Jinfeng Liu Jinfeng Liu Wenhui Liu Wenhui Liu Wenhui Liu Wenhui Liu Wenhui Liu Xinyi Huang Xinyi Huang Xinyi Huang Xinyi Huang Xinyi Huang Xiangchang Zeng Xiangchang Zeng Xiangchang Zeng Xiangchang Zeng Xiangchang Zeng Lulu Chen Zhenyu Li Dongsheng Ouyang Dongsheng Ouyang Dongsheng Ouyang Dongsheng Ouyang Dongsheng Ouyang Trimethylamine N-Oxide Exacerbates Renal Inflammation and Fibrosis in Rats With Diabetic Kidney Disease Frontiers in Physiology trimethylamine N-oxide diabetic kidney disease inflammation NLRP3 fibrosis |
| title | Trimethylamine N-Oxide Exacerbates Renal Inflammation and Fibrosis in Rats With Diabetic Kidney Disease |
| title_full | Trimethylamine N-Oxide Exacerbates Renal Inflammation and Fibrosis in Rats With Diabetic Kidney Disease |
| title_fullStr | Trimethylamine N-Oxide Exacerbates Renal Inflammation and Fibrosis in Rats With Diabetic Kidney Disease |
| title_full_unstemmed | Trimethylamine N-Oxide Exacerbates Renal Inflammation and Fibrosis in Rats With Diabetic Kidney Disease |
| title_short | Trimethylamine N-Oxide Exacerbates Renal Inflammation and Fibrosis in Rats With Diabetic Kidney Disease |
| title_sort | trimethylamine n oxide exacerbates renal inflammation and fibrosis in rats with diabetic kidney disease |
| topic | trimethylamine N-oxide diabetic kidney disease inflammation NLRP3 fibrosis |
| url | https://www.frontiersin.org/articles/10.3389/fphys.2021.682482/full |
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