Ezetimibe promotes CYP7A1 and modulates PPARs as a compensatory mechanism in LDL receptor-deficient hamsters

The LDL-C lowering effect of ezetimibe has been attributed primarily to increased catabolism of LDL-C via up-regulation of LDL receptor (LDLR) and decreased cholesterol absorption. Recently, ezetimibe has been demonstrated to have reverse cholesterol transport (RCT) promoting effects in mice, hamste...

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Published in:Lipids in health and disease 2020-02, Vol.19 (1), p.24-24, Article 24
Main Authors: Xia, Bin, Lin, Ping, Ji, Yubin, Yin, Jiayu, Wang, Jin, Yang, Xiaoqian, Li, Ting, Yang, Zixun, Li, Fahui, Guo, Shoudong
Format: Article
Language:English
Subjects:
Anticholesteremic agents
Antilipemic agents
Bile
Bile acids
Biological transport
Cardiovascular disease
Cholesterol
Cholesterol absorption
Chromatography
Cytochrome P-450
Deoxycholic acid
Diet
Drug therapy
Ezetimibe
Feces
Hamsters
Health aspects
High fat diet
Homeostasis
Hydroxylase
Hyperlipidemia
Kexin
Laboratory animals
LDL receptor
Lipid metabolism
Lipids
Lipoproteins
Liver
Low density lipoprotein
Low density lipoproteins
Metabolism
Niemann-Pick disease
Peroxisome proliferator-activated receptors
Pharmaceutical research
Polyclonal antibodies
Proprotein convertases
Protein binding
Protein expression
Protein turnover
Proteins
Reverse cholesterol transport
Sterol regulatory element-binding protein
Studies
Subtilisin
Testing
Triglycerides
Variance analysis
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Summary:The LDL-C lowering effect of ezetimibe has been attributed primarily to increased catabolism of LDL-C via up-regulation of LDL receptor (LDLR) and decreased cholesterol absorption. Recently, ezetimibe has been demonstrated to have reverse cholesterol transport (RCT) promoting effects in mice, hamsters and humans. However, the underlying mechanisms are still not clear. The aim of this study is to investigate whether ezetimibe improves RCT-related protein expression in LDLR hamsters. A high-fat diet was used to induce a human-like hyperlipidemia in LDLR hamsters. Lipid profiles were assayed by commercially available kits, and the effects of ezetimibe on lipid metabolism-related protein expression were carried out via western blot. Our data demonstrated that ezetimibe administration significantly reduced plasma total cholesterol (~ 51.6% reduction, P 
ISSN:1476-511X
1476-511X
DOI:10.1186/s12944-020-1202-5