Mechanisms of RSV-targeted SIRTs in the regulation of obesity.
| RSV-targeted SIRTS | Mechanisms of action | Regulation of substrates and pathways | Roles in diseases | Research objects | References |
|---|---|---|---|---|---|
| SIRT1 | ↑SIRT1↑FOXO1↑ATGL↑Lipolysis↓Lipid accumulation | RSV activates SIRT1, restores the expression of FOXO1 and ATGL, and thereby reverses fat accumulation. | Alleviates obesity by increasing lipid accumulation. | Male Sprague-Dawley rats and 3T3-L1 preadipocytes | [34] |
| SIRT1 | ↑SIRT1↑PGC-1α↑NFR-1/PPAR/PXR/PAR↑TFAM/UCP1 | RSV activates SIRT1, increases the level of UCP protein expression and TFAM, thereby enhancing energy expenditure. | Alleviates obesity by enhancing energy expenditure and thermogenesis. | Rats | [40] |
| SIRT1 | ↑SIRT1↓Akt2↓mTORC1↓p-mTOR↓p-S6K1↓Adipose inflammation | RSV inhibited adipose inflammation by activating the SIRT1/Akt2/mTOR/S6K1 pathway. | Alleviates obesity by inhibiting lipid accumulation. | Mice | [35] |
| SIRT1 | ↑4-HPA↑SIRT1↑PGC-1α/PPARγ/UCP1↑Mitochondrial biogenesis↑Browning of white adipocytes↓Lipogenesis | RSV is metabolized by the gut microbiota to produce 4-HPA and related metabolites, which activate the expression of SIRT1 pathway genes. | Inhibits obesity through gut microbiota-derived metabolic pathways. | Male C57BL/6J mice | [43] |
4-HPA: 4-hydroxyphenylacetic acid; Akt2: protein kinase B 2; ATGL: adipose triglyceride lipase; FOXO1: forkhead box O1; mTORC1: mechanistic target of rapamycin complex 1; NFR-1: nuclear factor related-1; PAR: poly (ADP-ribose); PGC-1α: peroxisome proliferator-activated receptor gamma coactivator 1-alpha; p-mTOR: phosphorylated mTOR; PPAR: peroxisome proliferator-activated receptor; p-S6K1: phosphorylated ribosomal protein S6 kinase beta-1; PXR: pregnane X receptor; RSV: resveratrol; SIRT: sirtuin; TFAM: mitochondrial transcription factor A; UCP: uncoupling protein.
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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