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Butyrate attenuates high-fat diet-induced glomerulopathy through GPR43-Sirt3 pathway

Published online by Cambridge University Press:  22 November 2024

Ying Shi ,
Lin Xing ,
Ruoyi Zheng ,
Xin Luo ,
Fangzhi Yue ,
Xingwei Xiang ,
Anqi Qiu ,
Junyan Xie ,
Ryan Russell  and
Dongmei Zhang Open the ORCID record for Dongmei Zhang [Opens in a new window]
Ying Shi
Affiliation:
Department of Endocrinology, Xiangya Hospital, Central South University, Changsha, People’s Republic of China
Lin Xing
Affiliation:
Department of Endocrinology, Xiangya Hospital, Central South University, Changsha, People’s Republic of China
Ruoyi Zheng
Affiliation:
Department of Endocrinology, Xiangya Hospital, Central South University, Changsha, People’s Republic of China
Xin Luo
Affiliation:
Department of Endocrinology, Xiangya Hospital, Central South University, Changsha, People’s Republic of China
Fangzhi Yue
Affiliation:
Department of Endocrinology, Xiangya Hospital, Central South University, Changsha, People’s Republic of China
Xingwei Xiang
Affiliation:
Department of Endocrinology, Xiangya Hospital, Central South University, Changsha, People’s Republic of China
Anqi Qiu
Affiliation:
Department of Endocrinology, Xiangya Hospital, Central South University, Changsha, People’s Republic of China
Junyan Xie
Affiliation:
Department of Endocrinology, Xiangya Hospital, Central South University, Changsha, People’s Republic of China
Ryan Russell
Affiliation:
Department of Health and Human Performance, College of Health Professions, University of Texas Rio Grande Valley, Brownsville, TX, USA
Dongmei Zhang*
Affiliation:
Department of Endocrinology, Xiangya Hospital, Central South University, Changsha, People’s Republic of China Hunan Engineering Research Center for Obesity and its Metabolic Complications, Xiangya Hospital, Central South University, Changsha, People’s Republic of China
*
Corresponding author: Dongmei Zhang; Email: [email protected]
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Abstract

The incidence of obesity-related glomerulopathy (ORG) is rising worldwide with very limited treatment methods. Paralleled with the gut–kidney axis theory, the beneficial effects of butyrate, one of the short-chain fatty acids (SCFA) produced by gut microbiota, on metabolism and certain kidney diseases have gained growing attention. However, the effects of butyrate on ORG and its underlying mechanism are largely unexplored. In this study, a mice model of ORG was established with a high-fat diet feeding for 16 weeks, and sodium butyrate treatment was initiated at the 8th week. Podocyte injury, oxidative stress and mitochondria function were evaluated in mice kidney and validated in vitro in palmitic acid-treated-mouse podocyte cell lines. Further, the molecular mechanisms of butyrate on podocytes were explored. Compared with controls, sodium butyrate treatment alleviated kidney injuries and renal oxidative stress in high-fat diet-fed mice. In mouse podocyte cell lines, butyrate ameliorated palmitic acid-induced podocyte damage and helped maintain the structure and function of the mitochondria. Moreover, the effects of butyrate on podocytes were mediated via the GPR43-Sirt3 signal pathway, as evidenced by the diminished effects of butyrate with the intervention of GPR43 or Sirt3 inhibitors. In summary, we conclude that butyrate has therapeutic potential for the treatment of ORG. It attenuates high-fat diet-induced ORG and podocyte injuries through the activation of the GPR43-Sirt3 signalling pathway.

Keywords

ButyrateMitochondriaObesity-related glomerulopathyPodocytes
Type
Research Article
Information
British Journal of Nutrition , Volume 133 , Issue 1 , 14 January 2025 , pp. 1 - 10
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Copyright
© The Author(s), 2024. Published by Cambridge University Press on behalf of The Nutrition Society

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