Curcumin regulates endogenous and exogenous metabolism via Nrf2-FXR-LXR pathway in NAFLD mice - 11/07/18
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Highlights |
• | Curcumin treatment improves the metabolism of nonalcoholic fatty liver mice. |
• | Curcumin activates the Nrf2/FXR/LXRα pathway to regulate metabolism of NAFLD mice. |
• | LXRα may be a novel therapeutic target of curcumin for the treatment of NAFLD. |
Abstract |
Background |
Curcumin is a natural polyphenol with beneficial effects on NAFLD patients and NAFLD is accompanied by metabolism decompensation.
Methods |
This study was focused on the effect of curcumin on the relationship between endogenous bile acids metabolism pathway and exogenous xenobiotics metabolism pathway in C57BL/6 mice of non-alcoholic fatty liver disease induced by high-fat and high-fructose diet (HFHFr) and in cultured mice hepatocytes.
Results |
Our results showed curcumin treatment apparently attenuated the hepatic steatosis and reversed the abnormalities of serum biochemical parameters in HFHFr-fed mice. Curcumin effectively reversed the expression of CYP3A and CYP7A in fatty liver status to restore metabolism capability. In the meantime, lipid synthesis has been controlled by curcumin, evidenced by the expression of CD36, SREBP-1c and FAS. Further, FXR, SHP and Nrf2 expressions were remarkably dropped in HFHFr-fed mice and LXRα expression was significantly enhanced, while curcumin treatment was quite effective to restore this pathway. In addition, LXRα antagonist GGPP pretreatment weakened the curcumin effects on CYP3A, CYP7A and SREBP-1c.
Conclusions |
These findings indicate that the Nrf2/FXR/LXRα pathway might synergistically regulate both endogenous and exogenous metabolism in NAFLD mice and LXRα may be a novel therapeutic target of curcumin for the prevention and treatment of NAFLD.
Le texte complet de cet article est disponible en PDF.Abbreviations : ACC, BA, CAR, DDI, FAS, GGPP, HFD, HNF-4, LXR, NAFLD, Nrf2, P450s, PA, PPAR, PXR, SHP, SREBP-1c, CYP3A, CYP7A1, CD36
Keywords : Curcumin, CYP3A, CYP7A, Metabolic regulation, Endogenous metabolism, Exogenous metabolism
Plan
Vol 105
P. 274-281 - septembre 2018 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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