Affiliation:
1. Basic Research Center of Traditional Chinese Medicine Prescription and Syndrome, Institute of Interdisciplinary Science Shanghai University of Traditional Chinese Medicine Shanghai 201203 China
2. Institute of Liver Disease, Shuguang Hospital Shanghai University of Traditional Chinese Medicine Shanghai 201203 China
3. Human Metabolomics Institute, Inc. Shenzhen 518109 Guangdong China
4. South China Normal University Guangzhou 510631 Guangdong China
5. Faculty of Food Science and Engineering Kunming University of Science and Technology Kunming 650500 China
Abstract
AbstractBackground and AimThe prevalence of nonalcoholic fatty liver disease (NAFLD) has been rising globally. NAFLD patients combined with cholestasis have more obvious liver fibrosis, impaired bile acid (BA), and fatty acid (FA) metabolism and severer liver injury; however, its therapeutic options are limited, and the underlying metabolic mechanisms are understood. Here, we aimed to investigate the effects of farnesoid X receptor (FXR) on BA and FA metabolism in NAFLD combined with cholestasis and related signaling pathways.MethodsA mouse model of NAFLD combined with cholestasis was established by joint intervention with high‐fat diet (HFD) and alpha‐naphthylisothiocyanate. The effects of FXR on BA and FA metabolism were evaluated by serum biochemical analysis. Liver damage was identified by histopathology. The expression of nuclear hormone receptor, membrane receptor, FA transmembrane transporter, and BA transporter protein in mice were measured by western blot.ResultsNAFLD mice combined with cholestasis developed more severe cholestasis and dysregulated BA and FA metabolism. Meanwhile, the expression of FXR protein was decreased in NAFLD mice combined with cholestasis compared to the controls. Fxr−/− mice showed liver injury. HFD aggravated the liver injury with decreased BSEP expression, increased expression of NTCP, LXRα, SREBP‐1c, FAS, ACC1, and CD36, and significantly increased BA and FA accumulation.ConclusionAll the results suggested that FXR plays a key role in both FA and BA metabolism in NAFLD combined with cholestasis and thus may be a potential target for the treatment of disorders of BA and FA metabolism in NAFLD combined with cholestasis.
Funder
National Natural Science Foundation of China
Subject
Gastroenterology,Hepatology
Cited by
1 articles.
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