Pravastatin activates the expression of farnesoid X receptor and liver X receptor alpha in Hep3B cells

Byun, Hyun Woo; Hong, Eun Mi; Park, Soo Hee; Koh, Dong Hee; Choi, Min Ho; Jang, Hyun Joo; Kae, Sea Hyub; Liu, Jin

doi:10.1016/s1499-3872(14)60009-6

Cited by 11 publications

(15 citation statements)

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“…It is known that both BA synthetic enzymes and BA transporters play an important role in BA homeostasis. The data of the present study showed that atorvastatin significantly increased the expression of Cyp7a1, confirming recent reports (Byun et al, 2014; Fu, Cui & Klaassen, 2014). The expression of Cyp7a1 is regulated by a mechanism involving the BA-activated farnesoid X receptor (FXR) in hepatocytes and enterocytes.…”

Section: Discussionsupporting

confidence: 93%

“…Hydrophobic BAs are potent inflammatory chemical that cause injury to liver (Chiang, 2013). In vitro and in vivo studies indicate that statins can alter BA metabolism in hepatocytes (Byun et al, 2014; Fu, Cui & Klaassen, 2014). The rate-limiting enzyme for the classic pathway of BA synthesis in the liver is Cyp7a1(Chiang, 2013).…”

Section: Introductionmentioning

confidence: 99%

“…The rate-limiting enzyme for the classic pathway of BA synthesis in the liver is Cyp7a1(Chiang, 2013). It has been reported that atorvastatin increases Cyp7a1, and alters the expression of Cyp7a1 regulatory genes, farnesoid X receptor (FXR) and small heterodimer partner (SHP) (Byun et al, 2014; Fu, Cui & Klaassen, 2014). BA transporters also play pivotal roles in maintaining BA homeostasis.…”

Section: Introductionmentioning

confidence: 99%

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Atorvastatin alters the expression of genes related to bile acid metabolism and circadian clock in livers of mice

et al. 2017

PeerJ

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AimAtorvastatin is a HMG-CoA reductase inhibitor used for hyperlipidemia. Atorvastatin is generally safe but may induce cholestasis. The present study aimed to examine the effects of atorvastatin on hepatic gene expression related to bile acid metabolism and homeostasis, as well as the expression of circadian clock genes in livers of mice.MethodsAdult male mice were given atorvastatin (10, 30, and 100 mg/kg, po) daily for 30 days, and blood biochemistry, histopathology, and gene expression were examined.ResultsRepeated administration of atorvastatin did not affect animal body weight gain or liver weights. Serum enzyme activities were in the normal range. Histologically, the high dose of atorvastatin produced scattered swollen hepatocytes, foci of feathery-like degeneration, together with increased expression of Egr-1 and metallothionein-1. Atorvastatin increased the expression of Cyp7a1 in the liver, along with FXR and SHP. In contract, atorvastatin decreased the expression of bile acid transporters Ntcp, Bsep, Ostα, and Ostβ. The most dramatic change was the 30-fold induction of Cyp7a1. Because Cyp7a1 is a circadian clock-controlled gene, we further examined the effect of atorvastatin on clock gene expression. Atorvastatin increased the expression of clock core master genes Bmal1 and Npas2, decreased the expression of clock feedback genes Per2, Per3, and the clock targeted genes Dbp and Tef, whereas it had no effect on Cry1 and Nr1d1 expression.ConclusionRepeated administration of atorvastatin affects bile acid metabolism and markedly increases the expression of the bile acid synthesis rate-limiting enzyme gene Cyp7a1, together with alterations in the expression of circadian clock genes.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Atorvastatin alters the expression of genes related to bile acid metabolism and circadian clock in livers of mice

et al. 2017

PeerJ

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“…Recently, growing evidence has shown that PPARα is implicated in metabolic processes of multiple lipids, including cholesterol, triglyceride, phospholipid, bile acids, and fatty acids (Table 1). NPC1L1 Upregulation, downregulation [22][23][24] ABCG5, ABCG8 Upregulation [25] Triglyceride metabolism LPL Upregulation [26][27][28] ApoA-V Upregulation [29,30] Angptl4 Upregulation [31,32] ApoC-III Downregulation [33] Phospholipid metabolism ABCB4 Upregulation [34,35] ABCA1 Upregulation [36] Bile acid metabolism…”

Section: Pparα and Lipid Metabolismmentioning

confidence: 99%

“…Mutations in SOD, GSH-Px, CAT Upregulation [50][51][52] VLDL metabolism MTP Upregulation [53] either ABCG5 or ABCG8 cause sitosterolemia. Treatment of Hep3B cells with pravastatin results in a significant increase in ABCG5 and ABCG8 levels, at least partially, by activating PPARα/liver X receptor α (LXRα) signaling pathway [25].…”

Section: Pparα Regulates Cholesterol Homeostasismentioning

confidence: 99%

Peroxisome Proliferator-Activated Receptor α in Lipid Metabolism and Atherosclerosis

Zheng

Tang

2015

Advances in Clinical Chemistry

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Statin therapy reduces plasma angiopoietin-like 3 (ANGPTL3) concentrations in hypercholesterolemic patients via reduced liver X receptor (LXR) activation

et al. 2020

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Pravastatin activates the expression of farnesoid X receptor and liver X receptor alpha in Hep3B cells

Cited by 11 publications

References 57 publications

Atorvastatin alters the expression of genes related to bile acid metabolism and circadian clock in livers of mice

Atorvastatin alters the expression of genes related to bile acid metabolism and circadian clock in livers of mice

Peroxisome Proliferator-Activated Receptor α in Lipid Metabolism and Atherosclerosis

Statin therapy reduces plasma angiopoietin-like 3 (ANGPTL3) concentrations in hypercholesterolemic patients via reduced liver X receptor (LXR) activation

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