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Succinate Induces Liver Damage and Hepatic Fibrosis in a Mouse Model

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Journal Title
Keimyung Med J
Issued Date
2022
Volume
41
Issue
2
Keyword
GPR91Liver fibrosisMouse modelSodium succinate dietSuccinate
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.
Type
Article
ISSN
2733-5380
Source
https://www.e-kmj.org/journal/view.php?number=2264
DOI
10.46308/kmj.2022.00143
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/44496
Appears in Collections:
2. Keimyung Medical Journal (계명의대 학술지) > 2022
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