首页|Alisol B 23-acetate promotes white adipose tissue browning to mitigate high-fat diet-induced obesity by regulating mTOR-SREBP1 signaling

Alisol B 23-acetate promotes white adipose tissue browning to mitigate high-fat diet-induced obesity by regulating mTOR-SREBP1 signaling

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Objective:Obesity is a global health concern with management strategies encompassing bariatric surgery and anti-obesity drugs;however,concerns regarding complexities and side effects persist,driving research for more effective,low-risk strategies.The promotion of white adipose tissue(WAT)browning has emerged as a promising approach.Moreover,alisol B 23-acetate(AB23A)has demonstrated efficacy in addressing metabolic disorders,suggesting its potential as a therapeutic agent in obesity management.Therefore,in this study,we aimed to investigate the therapeutic potential of AB23A for mitigating obesity by regulating metabolic phenotypes and lipid distribution in mice fed a high-fat diet(HFD).Methods:An obesity mouse model was established by administration of an HFD.Glucose and insulin metabolism were assessed via glucose and insulin tolerance tests.Adipocyte size was determined using hematoxylin and eosin staining.The expression of browning markers in WAT was evaluated using Western blotting and quantitative real-time polymerase chain reaction.Metabolic cage monitoring involved the assessment of various parameters,including food and water intake,energy metabolism,res-piratory exchange rates,and physical activity.Moreover,oil red O staining was used to evaluate intracel-lular lipid accumulation.A bioinformatic analysis tool for identifying the molecular mechanisms of traditional Chinese medicine was used to examine AB23A targets and associated signaling pathways.Results:AB23A administration significantly reduced the weight of obese mice,decreased the mass of inguinal WAT,epididymal WAT,and perirenal adipose tissue,improved glucose and insulin metabolism,and reduced adipocyte size.Moreover,treatment with AB23A promoted the expression of browning markers in WAT,enhanced overall energy metabolism in mice,and had no discernible effect on food intake,water consumption,or physical activity.In 3T3-L1 cells,AB23A inhibited lipid accumulation,and both AB23A and rapamycin inhibited the mammalian target of rapamycin-sterol regulatory element-binding protein-1(mTOR-SREBP1)signaling pathway.Furthermore,3-isobutyl-1-methylxanthine,dexamethasone and insulin,at concentrations of 0.25 mmol/L,0.25 μmol/L and 1 μg/mL,respectively,induced activation of the mTOR-SREBP1 signaling pathway,which was further strength-ened by an mTOR activator MHY1485.Notably,MHY1485 reversed the beneficial effects of AB23A in 3T3-L1 cells.Conclusion:AB23A promoted WAT browning by inhibiting the mTOR-SREBP1 signaling pathway,offering a potential strategy to prevent obesity.

ObesityAlisol B 23-acetateAdipose tissuemTOR-SREBP1High-fat diet

Lu-lu Han、Xin Zhang、Hui Zhang、Ting Li、Yi-chen Zhao、Ming-hui Tian、Feng-lei Sun、Bo Feng

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Department of Neurology Three,The Fifth People's Hospital of Jinan,Jinan 250013,Shandong Province,China

Department of Gastroenterology,Affiliated Hospital of Shandong University of Traditional Chinese Medicine,Jinan 250014,Shandong Province,China

The First Clinical Medical College,Shandong University of Traditional Chinese Medicine,Jinan 250014,Shandong Province,China

Department of Geriatrics,the First Affiliated Hospital of Shandong First Medical University(Shandong Provincial Qianfoshan Hospital),Jinan 250014,Shandong Province,China

Chinese Medicine Culture and Literature Research Institute,Shandong University of Traditional Chinese Medicine,Jinan 250014,Shandong Province,China

Department of General Medicine,Affiliated Hospital of Shandong University of Traditional Chinese Medicine,Jinan 250014,Shandong Province,China

Department of Traditional Chinese Medicine,the Second People's Hospital of Haibei Prefecture,Zangzu Autonomous Prefecture of Haibei,810300,Qinghai Province,China

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Shandong Provincial Natural Science Foundation General ProgramShandong Provincial Traditional Chinese Medicine Science and Technology Project General ProgramJinan Clinical Medical Science and Technology Innovation ProgramQinghai Province Highend Innovative Talents Thousand Talents Program

ZR2022MH213M2023241202328013

2024

10.1016/j.joim.2024.01.003

结合医学学报(英文版)
上海市中西医结合学会,上海长海医院

结合医学学报(英文版)

CSTPCD
影响因子：0.711
ISSN：2095-4964
年,卷(期)：2024.22(1)
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