Obeticholic acid protects mice against lipopolysaccharide-induced liver injury and inflammation - 15/12/17
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| Iconographies | 6 |
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| Autres | 0 |
Highlights |
• | FXR agonist OCA pretreatment protects mice from LPS-induced acute liver injury. |
• | Orally OCA pretreatment at 5 mg/kg once daily for 5 days stimulates the expression of FXR and BSEP in livers. |
• | Orally OCA pretreatment suppresses the expression of TNF-α, IL-1β and IL-6 in livers of mice treated with LPS for 48h. |
• | Orally OCA pretreatment induces autophagy activity associated with higher expression of ATF4 in livers of mice. |
Abstract |
Background |
Cholestasis, as a main manifestation, induces liver injury during sepsis. The farnesoid X receptor (FXR) plays an important role in regulating bile acid homeostasis. Whether FXR activation by its agonist obeticholic acid (OCA) is contributed to improve sepsis-induced liver injury remains unknown.
Objective |
The aim of the present study was to investigate the effect of OCA on lipopolysaccharide (LPS)-induced acute liver injury in mice.
Results |
8-week old male C57BL/6J mice were randomly divided into control group, LPS group, oral OCA group and LPS plus oral OCA (LPS + OCA) group. The serum and livers were collected for further analysis. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bile acid (TBA) and total bilirubin (TBIL) were measured at indicated time after LPS administration. Liver sections were stained with hematoxylin & eosin (H&E). Orally OCA pretreatment stimulated the expression of FXR and BSEP in livers and protected mice from LPS-induced hepatocyte apoptosis and inflammatory infiltration. Consistently, LPS-induced higher serum levels of ALT, AST, TBA and TBIL were significantly reversed by OCA administration. Meanwhile, the mRNA levels of interleukin 1β (IL-1β), tumor necrosis factor α (TNF-α) and IL-6 were decreased in livers of mice in LPS + OCA group compared with LPS group. Further investigation indicated that the higher expression of ATF4 and LC3II/I were associated with the protective effect of OCA on LPS-induced liver injury.
Conclusion |
Orally OCA pretreatment protects mice from LPS-induced liver injury possibly contributed by improved bile acid homeostasis, decreased inflammatory factors and ATF4-mediated autophagy activity in hepatocytes.
Le texte complet de cet article est disponible en PDF.Abbreviations : FXR, OCA, LPS, ALT, AST, TBA, TBIL, ICU, CYP7A1, TNF-α, IL-1β, ATF4
Keywords : Obeticholic acid, Liver injury, FXR, ATF4, Autophagy
Plan
Vol 96
P. 1292-1298 - décembre 2017 Retour au numéro
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