Effect of resveratrol on key signaling pathways including SIRT1/AMPK/Smad3/TGF-β and miRNA-141 related to NAFLD in an animal model

Sahar Yarahmadi , Mohammadjavad Sotoudeheian, Navid Farahmandian, Yaser Mohammadi, Mehdi Koushki, Esmaeel Babaeenezhad, Zeynab Yousefi, Soudabeh Fallah

Abstract


Background and purpose: Non-alcoholic fatty liver disease (NAFLD) is a chronic metabolic condition characterized by the accumulation of excess fat in the liver, which can ultimately lead to fibrosis and cirrhosis. This study investigated the impact of resveratrol on the signaling pathways miR-141/SIRT1/AMPK/TGF-β/Smad3 in fatty liver of male C57/BL6 mice.

Experimental approach: Twenty-one male C57/BL6 mice were acclimatized for 10 days and divided into               3 groups (n = 7), including control, NAFLD, and NAFLD + resveratrol groups. After an 8-week HFD to induce NAFLD, the mice were treated with resveratrol (100 mg/kg/day; oral gavage) for 8 weeks. At the end of the study (16 weeks), serum and liver tissue samples were collected. Gene expression was assessed using RT-PCR, while protein levels were analyzed via Western blotting. Statistical analysis was performed using SPSS 16.

Findings/Results: The results of the study showed that the expression levels of the genes Smad3 and miRNA-141 were significantly reduced in the resveratrol-treated group compared to the NAFLD group, while the expression levels of SIRT1 and TGF-β were significantly increased. In addition, the Western blot results indicated that the levels of the proteins P-AMPK and SIRT1 in the resveratrol-treated group were significantly higher compared to the NAFLD group. Furthermore, a significant reduction in fat accumulation and degeneration was observed in the histopathological findings of the liver in the resveratrol-treated group.

Conclusion and implications: The study concluded that resveratrol has the potential to reduce liver damage from NAFLD by modulating various signaling pathways, particularly TGF-β/Smad3, SIRT1/AMPK, and miRNA-141, leading to improved lipid metabolism and reduced hepatic steatosis. While the findings underscored the multifaceted therapeutic effects of resveratrol, further research and clinical trials are necessary to fully understand its mechanisms and applications in humans.

 

 


Keywords


miRNA-141; Non-alcoholic fatty liver disease; Resveratrol; SIRT1; TGF-β.

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