Resveratrol Ameliorates Obesity by Targeting NDUFS8/HMGB1 to Promote Adipocyte Browning and Inhibiting Adipose Inflammation
10.13422/j.cnki.syfjx.20260501
- VernacularTitle:白藜芦醇通过靶向NDUFS8/HMGB1调控线粒体功能促进脂肪棕色化改善脂肪炎症治疗肥胖作用机制
- Author:
Zedong WANG
1
;
Xianyu XU
2
;
Linlin LI
2
;
Yongping ZHU
2
;
Junzhe ZHANG
2
;
Liwei GU
2
;
Yanqing LIU
2
;
Nan TONG
3
;
Shengnan SHEN
2
;
Yibai XIONG
2
;
Jigang WANG
1
Author Information
1. School of Pharmacy， Chengdu University of Traditional Chinese Medicine， Chengdu 611137， China
2. Institute of Chinese Materia Medica， China Academy of Chinese Medical Sciences，Beijing 100700，China
3. Dongzhimen Hospital，Beijing University of Chinese Medicine，Beijing 100007，China
- Publication Type:Journal Article
- Keywords:
chemical proteomics;
resveratrol （Res）;
lipid accumulation;
NADH-ubiquinone oxidoreductase core subunit S8 （NDUFS8）;
high-mobility group protein B1 （HMGB1）
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2026;32(23):136-143
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo identify the direct target proteins for the anti-obesity effect of resveratrol （Res） via chemical proteomic analysis and systematically explore the molecular mechanisms by which Res inhibits lipid accumulation in adipocytes from mitochondrial function regulation， adipocyte browning， and inflammation inhibition， thus providing new targets and experimental evidence for the prevention and treatment of obesity and related metabolic diseases. MethodsThe cell counting kit-8 （CCK-8） assay was adopted to detect the safe and effective doses （7.5， 15， 30 μmol·L-1） of Res for treating 3T3-L1 cells based on the cell survival rate. After being induced to differentiate into mature adipocytes， the cells were assigned into the blank ［treated with dimethyl sulfoxide （DMSO）］ group and the Res （7.5， 15， 30 μmol·L-1） groups and treated for 48 h. Oil red O staining and total triglyceride （TG） content were assessed to measure lipid accumulation in adipocytes. Target protein identification of Res was conducted through IAA-P-based chemical proteomics combined with high-resolution mass spectrometry. Target proteins of Res were validated by cellular thermal shift assay （CETSA） combined with Western blot analysis. Furthermore， the expression of browning markers peroxisome proliferator-activated receptor γ coactivator-1α （PGC-1α） and mitochondrial uncoupling protein 1 （UCP1）， as well as the target proteins NADH-ubiquinone oxidoreductase core subunit S8 （NDUFS8） and high-mobility group protein B1 （HMGB1） were determined by Western blot. The ATP assay kit was used to measure the ATP concentration. Mitochondrial biogenesis was characterized with MitoTracker Green， on the basis of which the regulatory effect of Res on mitochondrial function was analyzed. The level of the inflammatory cytokine tumor necrosis factor-α （TNF-α） was measured by enzyme-linked immunosorbent assay （ELISA）， on the basis of which the anti-inflammatory effect of Res on adipocytes was evaluated. ResultsCompared with the control group， Res demonstrated safety and efficacy within the range of 7.5-30 μmol·L-1， without significantly affecting cell viability. Compared with the control group， different concentrations of Res reduced lipid accumulation in 3T3-L1 adipocytes （P<0.01）， promoted the expression of NDUFS8 （P<0.01）， increased the ATP concentration and the protein levels of UCP1 and PGC-1α， elevated the level of TNF-α （P<0.05， P<0.01）. ConclusionNDUFS8 and HMGB1were identified as the target proteins of Res in mitigating obesity. Res promotes mitochondrial biogenesis to induce the browning of 3T3-L1 adipocytes via targeting NDUFS8 and it inhibits the TNF-α-mediated inflammatory signaling via targeting HMGB1， thus inhibiting lipid accumulation and ameliorating obesity.
