Frontiers in Physiology (Jun 2021)
Trimethylamine N-Oxide Exacerbates Renal Inflammation and Fibrosis in Rats With Diabetic Kidney Disease
- 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
Affiliations
- Qing Fang
- Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China
- Qing Fang
- Hunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology, Central South University, Changsha, China
- Qing Fang
- Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, China
- Qing Fang
- National Clinical Research Center for Geriatric Disorders, Changsha, China
- Qing Fang
- Hunan Key Laboratory for Bioanalysis of Complex Matrix Samples, Changsha Duxact Biotech Co., Ltd., Changsha, China
- Binjie Zheng
- Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China
- Binjie Zheng
- Hunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology, Central South University, Changsha, China
- Binjie Zheng
- Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, China
- Binjie Zheng
- National Clinical Research Center for Geriatric Disorders, Changsha, China
- Binjie Zheng
- Hunan Key Laboratory for Bioanalysis of Complex Matrix Samples, Changsha Duxact Biotech Co., Ltd., Changsha, China
- Na Liu
- Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China
- Na Liu
- Hunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology, Central South University, Changsha, China
- Na Liu
- Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, China
- Na Liu
- National Clinical Research Center for Geriatric Disorders, Changsha, China
- Na Liu
- Hunan Key Laboratory for Bioanalysis of Complex Matrix Samples, Changsha Duxact Biotech Co., Ltd., Changsha, China
- Jinfeng Liu
- Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China
- Jinfeng Liu
- Hunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology, Central South University, Changsha, China
- Jinfeng Liu
- Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, China
- Jinfeng Liu
- National Clinical Research Center for Geriatric Disorders, Changsha, China
- Jinfeng Liu
- Hunan Key Laboratory for Bioanalysis of Complex Matrix Samples, Changsha Duxact Biotech Co., Ltd., Changsha, China
- Wenhui Liu
- Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China
- Wenhui Liu
- Hunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology, Central South University, Changsha, China
- Wenhui Liu
- Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, China
- Wenhui Liu
- National Clinical Research Center for Geriatric Disorders, Changsha, China
- Wenhui Liu
- Hunan Key Laboratory for Bioanalysis of Complex Matrix Samples, Changsha Duxact Biotech Co., Ltd., Changsha, China
- Xinyi Huang
- Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China
- Xinyi Huang
- Hunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology, Central South University, Changsha, China
- Xinyi Huang
- Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, China
- Xinyi Huang
- National Clinical Research Center for Geriatric Disorders, Changsha, China
- Xinyi Huang
- Hunan Key Laboratory for Bioanalysis of Complex Matrix Samples, Changsha Duxact Biotech Co., Ltd., Changsha, China
- Xiangchang Zeng
- Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China
- Xiangchang Zeng
- Hunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology, Central South University, Changsha, China
- Xiangchang Zeng
- Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, China
- Xiangchang Zeng
- National Clinical Research Center for Geriatric Disorders, Changsha, China
- Xiangchang Zeng
- Hunan Key Laboratory for Bioanalysis of Complex Matrix Samples, Changsha Duxact Biotech Co., Ltd., Changsha, China
- Lulu Chen
- Hunan Key Laboratory for Bioanalysis of Complex Matrix Samples, Changsha Duxact Biotech Co., Ltd., Changsha, China
- Zhenyu Li
- Department of Geriatric Medicine, Xiangya Hospital, Central South University, Changsha, China
- Dongsheng Ouyang
- Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China
- Dongsheng Ouyang
- Hunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology, Central South University, Changsha, China
- Dongsheng Ouyang
- Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, China
- Dongsheng Ouyang
- National Clinical Research Center for Geriatric Disorders, Changsha, China
- Dongsheng Ouyang
- Hunan Key Laboratory for Bioanalysis of Complex Matrix Samples, Changsha Duxact Biotech Co., Ltd., Changsha, China
- DOI
- https://doi.org/10.3389/fphys.2021.682482
- Journal volume & issue
-
Vol. 12
Abstract
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.
Keywords
