Keimyung Med J.
2022 Dec;41(2):84-91. 10.46308/kmj.2022.00143.
Succinate Induces Liver Damage and Hepatic Fibrosis in a Mouse Model
- Affiliations
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- 1Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon, Korea
- 2Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
- 3Department of Physiology, Kangwon National University School of Medicine, Chuncheon, Korea
- 4Department of Nutritional Sciences, University of Connecticut, Storrs, Connecticut, USA
- KMID: 2536901
- DOI: http://doi.org/10.46308/kmj.2022.00143
Abstract
- Hepatic stellate cells (HSCs) play a key role in liver fibrosis. Succinate and succinate receptor (GPR91) signaling pathway are involved in the activation, proliferation, and migration of HSCs. We investigated whether succinate may induce hepatic fibrosis. The mice were randomly divided into 2 groups —the control group (chow diet-fed mice, n = 26) and sodium succinate group (2% sodium succinate + chow diet, n = 38). Each diet was provided for 16 weeks. Mice administered an oral diet of 2% sodium succinate for sixteen weeks lost body weight and had increased serum alanine transaminase and hepatic triglyceride contents compared to those in the control mice. Moreover, mice fed with sodium succinate showed increased expression of the alpha smooth muscle actin protein and gene in the liver at 8 weeks of feeding and increased fibrosis in their histology at 16 weeks of feeding. However, the expression of the GPR91 protein and mRNA increased at 4 weeks of feeding, but decreased at 8 and 16 weeks of feeding. These results suggest that an oral succinate diet could induce liver damage and liver fibrosis in mice and that GPR91 signaling might be an early marker or sensor of hepatic fibrosis development.
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