Resveratrol suppresses hepatic fatty acid synthesis and increases fatty acid &beta;-oxidation via the microRNA-33/SIRT6 signaling pathway

Liu,Chunqiao; Pan,Xinyan; Hao,Zhihua; Wang,Xing; Wang,Chao; Song,Guangyao

doi:10.3892/etm.2024.12615

Resveratrol suppresses hepatic fatty acid synthesis and increases fatty acid β-oxidation via the microRNA-33/SIRT6 signaling pathway

Authors:
- Chunqiao Liu
- Xinyan Pan
- Zhihua Hao
- Xing Wang
- Chao Wang
- Guangyao Song
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Affiliations: Department of Internal Medicine, Hebei Medical University, Shijiazhuang, Hebei 050000, P.R. China, Department of Health Care, Hebei General Hospital, Shijiazhuang, Hebei 050051, P.R. China, Hebei Key Laboratory of Metabolic Diseases, Hebei General Hospital, Shijiazhuang, Hebei 050051, P.R. China
Published online on: June 19, 2024 https://doi.org/10.3892/etm.2024.12615
Article Number: 326
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Hyperlipidemia is a strong risk factor for numerous diseases. Resveratrol (Res) is a non-flavonoid polyphenol organic compound with multiple biological functions. However, the specific molecular mechanism and its role in hepatic lipid metabolism remain unclear. Therefore, the aim of the present study was to elucidate the mechanism underlying how Res improves hepatic lipid metabolism by decreasing microRNA-33 (miR-33) levels. First, blood miR-33 expression in participants with hyperlipidemia was detected by reverse transcription-quantitative PCR, and the results revealed significant upregulation of miR-33 expression in hyperlipidemia. Additionally, after transfection of HepG2 cells with miR-33 mimics or inhibitor, western blot analysis indicated downregulation and upregulation, respectively, of the mRNA and protein expression levels of sirtuin 6 (SIRT6). Luciferase reporter analysis provided further evidence for binding of miR-33 with the SIRT6 3'-untranslated region. Furthermore, the levels of peroxisome proliferator-activated receptor-γ (PPARγ), PPARγ-coactivator 1α and carnitine palmitoyl transferase 1 were increased, while the concentration levels of acetyl-CoA carboxylase, fatty acid synthase and sterol regulatory element-binding protein 1 were decreased when SIRT6 was overexpressed. Notably, Res improved the basic metabolic parameters of mice fed a high-fat diet by regulating the miR-33/SIRT6 signaling pathway. Thus, it was demonstrated that the dysregulation of miR-33 could lead to lipid metabolism disorders, while Res improved lipid metabolism by regulating the expression of miR-33 and its target gene, SIRT6. Thus, Res can be used to prevent or treat hyperlipidemia and associated diseases clinically by suppressing hepatic fatty acid synthesis and increasing fatty acid β-oxidation.

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