THE ROLE AND MECHANISM OF CURCUMIN IN REGULATING THE SIRT1/FOXO1 SIGHALING PATHWAY TO PREVENT NONALCOHOLIC FATTY LIVER DISEASE

JI Zhe; CAO Jian-min; WANG Li; WANG Ying; QIN Fei; ZHOU Hai-tao

Acta Nutrimenta Sinica ›› 2024, Vol. 46 ›› Issue (3) : 263-269.

JI Zhe¹, CAO Jian-min², WANG Li², WANG Ying¹, QIN Fei³, ZHOU Hai-tao³

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Abstract

Objective To investigate the effect and mechanism of curcumin on nonalcoholic fatty liver disease (NAFLD) via regulating silent mating-type information regulation 2 homolog 1(SIRT1)/ forkhead box protein O1 (FoxO1) signal pathway in HepG2 cells. Methods HepG2 cells were induced by fatty acids for 24 hours to establish an in vitro model of NAFLD. After staining with oil red O, the cellular steatosis was observed under light microscope, and the formation of autophage was observed under transmission electron microscope. The levels of total cholesterol (TC) and triglyceride (TG) in cells were measured by colorimetry. The expressions of SIRT1, acetylated forkhead box protein O1 (AC-FoxO1), microtubule-associated protein 1 light chain 3 (LC3), sequestosome 1 (SQSTM1/P62) and autophagy related protein 7 (ATG7) were detected by Western blot. The co-localization of SIRT1 and FoxO1 proteins in cells was observed by immunofluorescence. Results Curcumin could improve cellular steatosis, increase autophagy, and significantly reduce the contents of TC and TG and the expressions of AC-FoxO1 and P62 proteins (P<0.01). The protein expressions of SIRT1, ATG7 and the ratio of LC3-Ⅱ/LC3-Ⅰ were significantly increased (P<0.01). Curcumin also enhanced nuclear localization of FoxO1 in cells by activating SIRT1. By interfering with the expression of SIRT1, a large number of FoxOl migrated into the cytoplasmic region, and the co-localization of SIRT1 and FoxOl decreased. Conclusion Curcumin prevents NAFLD by regulating SIRT1/FoxO1 pathway, in which curcumin can promote the deacetylation of FoxO1, induce autophagy, and improve hepatocyte steatosis by activating SIRT1.

Key words

curcumin / nonalcoholic fatty liver disease (NAFLD) / silent mating-type information regulation 2 homolog 1(SRIT1) / forkhead box protein O1 (FoxO1) / autophagy

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JI Zhe, CAO Jian-min, WANG Li, WANG Ying, QIN Fei, ZHOU Hai-tao. THE ROLE AND MECHANISM OF CURCUMIN IN REGULATING THE SIRT1/FOXO1 SIGHALING PATHWAY TO PREVENT NONALCOHOLIC FATTY LIVER DISEASE[J]. Acta Nutrimenta Sinica. 2024, 46(3): 263-269

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