Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Nov;396(11):3135-3148.
doi: 10.1007/s00210-023-02520-7. Epub 2023 May 20.

A novel combination of metformin and resveratrol alleviates hepatic steatosis by activating autophagy through the cAMP/AMPK/SIRT1 signaling pathway

Havva Afshari  1 , Shokoofe Noori  2 , Afshin Zarghi  3
Affiliations

A novel combination of metformin and resveratrol alleviates hepatic steatosis by activating autophagy through the cAMP/AMPK/SIRT1 signaling pathway

Havva Afshari et al. Naunyn Schmiedebergs Arch Pharmacol. 2023 Nov.

Abstract

Nonalcoholic fatty liver disease (NAFLD) is a prevalent liver disorder that is associated with the accumulation of triglycerides (TG) in hepatocytes. Resveratrol (RSV), as a natural product, and metformin have been reported to have potential lipid-lowering effects for the treatment of NAFLD via autophagy, but the combined effects of both have not yet been studied. The current study aimed to investigate the role of autophagy in the lipid-lowering effects of RSV, alone and in combination with metformin, on the hepatic steatosis model of HepG2 cells and elucidate the mechanism of action. Triglyceride measurement and real-time PCR showed that RSV-metformin reduced lipid accumulation and the expression of lipogenic genes in palmitic acid (PA)-induced HepG2 cells. Additionally, the LDH release assay indicated that this combination protected HepG2 cells against PA-induced cell death through autophagy. The western blotting analysis revealed that RSV-metformin induced autophagy by reducing the expression of p62 and increasing LC3-I and LC3-II proteins. This combination also enhanced cAMP, phosphorylated AMP-activated protein kinase (p-AMPK), and Beclin-1 levels in HepG2 cells. Furthermore, SIRT1 inhibitor treatment inhibited autophagy induced by RSV-metformin, which indicated the autophagy induction is SIRT1-dependent. This study demonstrated for the first time that RSV-metformin reduced hepatic steatosis by triggering autophagy via the cAMP/AMPK/SIRT1 signaling pathway.

Keywords: AMPK; Autophagy; Metformin; NAFLD; Resveratrol; SIRT1; cAMP.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

References

    1. Aguirre L, Portillo MP, Hijona E, Bujanda L (2014) Effects of resveratrol and other polyphenols in hepatic steatosis. World J Gastroenterol: WJG 20(23):7366 - PubMed - PMC - DOI
    1. Ahmed MH, Byrne CD (2007) Modulation of sterol regulatory element binding proteins (SREBPs) as potential treatments for non-alcoholic fatty liver disease (NAFLD). Drug Discovery Today 12(17–18):740–747 - PubMed - DOI
    1. Ahmed LA, Salem MB, El-Din SHS, El-Lakkany NM, Ahmed HO, Nasr SM et al (2020) Gut microbiota modulation as a promising therapy with metformin in rats with non-alcoholic steatohepatitis: role of LPS/TLR4 and autophagy pathways. Eur J Pharmacol 887:173461 - PubMed - DOI
    1. A Al Saedi A C Goodman E D Myers A Hayes G Duque 2020 Rapamycin affects palmitate-induced lipotoxicity in osteoblasts by modulating apoptosis and autophagy The Journals of Gerontology: Series A 75 1 58 63
    1. Allaire M, Rautou P-E, Codogno P, Lotersztajn S (2019) Autophagy in liver diseases: time for translation? J Hepatol 70(5):985–998 - PubMed - DOI

LinkOut - more resources