The role of the RSV-SIRT axis in the treatment of MASLD.
| RSV-targeted SIRTS | Mechanisms of action | Regulation of substrates and pathways | Roles in diseases | Research objects | References |
|---|---|---|---|---|---|
| Not applicable | ↑Thrombospondin-2 as a predictive biomarker | Thrombospondin-2 levels correlate with HCC risk after HCV cure. | Predicts HCC occurrence post-DAA treatment. | HCV-infected patients treated with DAAs | [72] |
| SIRT1 | ↑SIRT1↓Lipogenesis↓Inflammation | RSV activates SIRT1, which decreases lipogenesis and inflammation. | Alleviates hepatic steatosis in obese mice. | High-fat diet-fed mice | [73] |
| SIRT1 | ↑SIRT1↓TGF-β/Smad signaling | SIRT1 activation inhibits TGF-β/Smad pathway. | Ameliorates liver fibrosis. | Rhesus monkeys with liver fibrosis; aged rats with liver fibrosis | [71] |
| SIRT1 | ↑SIRT1↓p53-related senescence↓NLRP3 inflammation | Deacetylation of HnRNP U by SIRT1 inhibits cellular senescence and suppresses NLRP3 inflammasome activation in liver fibrosis. | Contributes to the amelioration of liver fibrosis. | Aged rats with liver fibrosis | [81] |
| SIRT1-independent | ↑OBRb expression, ↑Leptin sensitivity | RSV increases long-form OBRb content, enhancing leptin-induced STAT3 phosphorylation and reducing triglyceride accumulation. | Improves hepatic steatosis by restoring leptin signaling. | Palmitate-induced steatotic HepG2 cells | [77] |
| SIRT1 | ↑SIRT1 activity↓STAT3 phosphorylation↓HSC proliferation | Pterostilbene (RSV analog) inhibits excessive proliferation of activated HSCs through crosstalk between SIRT1 and STAT3 pathways. | Alleviates liver fibrosis by reducing HSC activation. | Activated HSCs | [79] |
| SIRT1 | ↑SIRT1, regulation of SREBPs↓Lipid synthesis | SIRT1 regulates SREBPs to control lipid metabolism. | Contributes to the improvement of NAFLD and metabolic syndrome. | Palmitate-induced steatotic HepG2 cells | [77] |
| SIRT1 | ↑SIRT1, deacetylation of PGC-1α↑Mitochondrial fatty acid oxidation | SIRT1-mediated deacetylation of PGC-1α improves mitochondrial fatty acid oxidation. | Alleviates hepatic steatosis in type 2 diabetes. | Animal model of type 2 diabetes mellitus with hepatic steatosis | [75] |
DAAs: direct-acting antivirals; HCC: hepatocellular carcinoma; HCV: hepatitis C virus; HnRNP U: heterogeneous nuclear ribonucleoprotein U; HSCs: hepatic stellate cells; MASLD: metabolic dysfunction-associated steatotic liver disease; NAFLD: non-alcoholic fatty liver disease; NLRP3: NOD-like receptor family, pyrin domain-containing 3; OBRb: leptin receptor isoform b; p53: tumor protein p53; PGC-1α: peroxisome proliferator-activated receptor gamma coactivator 1-alpha; RSV: resveratrol; SIRT: sirtuin; SREBPs: sterol regulatory element-binding proteins; STAT3: signal transducer and activator of transcription 3; TGF-β: transforming growth factor-β.
JY: Data curation, Formal analysis, Investigation, Methodology, Writing—original draft, Writing—review & editing. SC: Data curation, Formal analysis, Investigation, Methodology, Writing—original draft, Writing—review & editing. TZ: Data curation, Formal analysis, Investigation, Methodology, Writing—original draft, Writing—review & editing. YZ: Data curation, Formal analysis, Investigation, Methodology, Writing—original draft, Writing—review & editing. ZL: Data curation, Formal analysis, Investigation, Methodology, Writing—original draft, Writing—review & editing. HL: Conceptualization, Investigation, Writing—review & editing, Supervision. All authors read and approved the submitted version.
The authors declare that there are no conflicts of interest.
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This work was supported by a grant from the Natural Science Foundation of Shandong Province, China [No. ZR2025MS387]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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