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14-Deoxygarcinol improves insulin sensitivity in high-fat diet-induced obese mice via mitigating NF-kappa B/Sirtuin 2-NLRP3-mediated adipose tissue remodeling

文献类型：期刊论文

作者Chen, Jia-li5; Feng, Zhe-ling3,4,5; Zhou, Fei5; Lou, Ruo-han5; Peng, Cheng2; Ye, Yang3,4; Lin, Li-gen1,5
刊名ACTA PHARMACOLOGICA SINICA
出版日期2022-08-09
页码12
关键词14-deoxygarcinol adipose tissue inflammation insulin resistance interleukin-1 beta NLRP3 inflammasome Sirtuin 2
ISSN号1671-4083
DOI10.1038/s41401-022-00958-8
通讯作者Lin, Li-gen(ligenl@um.edu.mo)
英文摘要Interleukin (IL)-1 beta is a culprit of adipose tissue inflammation, which in turn causes systematic inflammation and insulin resistance in obese individuals. IL-1 beta is mainly produced in monocytes and macrophages and marginally in adipocytes, through cleavage of the inactive pro-IL-1 beta precursor by caspase-1, which is activated via the NLRP3 inflammasome complex. The nuclear factor-kappa B (NF-kappa B) transcription factor is the master regulator of inflammatory responses. Brindle berry (Garcinia cambogia) has been widely used as health products for treating obesity and related metabolic disorders, but its active principles remain unclear. We previously found a series of polyisoprenylated benzophenones from brindle berry with anti-inflammatory activities. In this study we investigated whether 14-deoxygarcinol (DOG), a major polyisoprenylated benzophenone from brindle berry, alleviated adipose tissue inflammation and insulin sensitivity in high-fat diet fed mice. The mice were administered DOG (2.5, 5 mg . kg(-1) . d(-)(1), i.p.) for 4 weeks. We showed that DOG injection dose-dependently improved insulin resistance and hyperlipidemia, but not adiposity in high-fat diet-fed mice. We found that DOG injection significantly alleviated adipose tissue inflammation via preventing macrophage infiltration and pro-inflammatory polarization of macrophages, and adipose tissue fibrosis via reducing the abnormal deposition of extracellular matrix. In LPS plus nigericin-stimulated NP-1 macrophages, DOG (1.25, 2.5, 5 mu M) dose-dependently suppressed the activation of NLRP3 inflammasome and NF-KB signaling pathway. We demonstrated that DOG bound to and activated the deacetylase Sirtuin 2, which in turn deacetylated and inactivated NLRP3 inflammasome to reduce IL-1 beta secretion. Moreover, DOG (1.25, 2.5, 5 mu M) dose-dependently mitigated inflammatory responses in macrophage conditioned media-treated adipocytes and suppressed macrophage migration toward adipocytes. Taken together, DOG might be a drug candidate to treat metabolic disorders through modulation of adipose tissue remodeling.
WOS关键词CHRONIC INFLAMMATION ; OXIDATIVE STRESS ; METABOLISM ; ACTIVATION ; RESISTANCE ; INTERLEUKIN-1-BETA ; INHIBITION ; FIBROSIS ; GARCINOL ; MATRIX
资助项目National Natural Science Foundation of China[81872754] ; Research Fund of University of Macau[MYRG2020-00091-ICMS] ; Science and Technology Development Fund, Macao SAR[FDCT 0064/2021/AGJ] ; Internal Research Grant of the State Key Laboratory of Quality Research in Chinese Medicine, University of Macau[QRCM-IRG2022-014] ; Open Research Fund of Chengdu University of Traditional Chinese Medicine Key Laboratory of Systematic Research of Distinctive Chinese Medicine Resources in Southwest China
WOS研究方向Chemistry ; Pharmacology & Pharmacy
语种英语
WOS记录号WOS:000839461400002
出版者NATURE PUBL GROUP
源URL[http://119.78.100.183/handle/2S10ELR8/302308]  
专题新药研究国家重点实验室
通讯作者Lin, Li-gen
作者单位1.Univ Macau, Fac Hlth Sci, Dept Pharmaceut Sci, Macau, Peoples R China
2.Chengdu Univ Tradit Chinese Med, Sch Pharm, State Key Lab Southwestern Chinese Med Resources, Chengdu 610075, Peoples R China
3.Chinese Acad Sci, Shanghai Inst Mat Med, Nat Prod Chem Dept, Shanghai 201203, Peoples R China
4.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
5.Univ Macau, Inst Chinese Med Sci, State Key Lab Qual Res Chinese Med, Macau, Peoples R China
推荐引用方式
GB/T 7714		 Chen, Jia-li,Feng, Zhe-ling,Zhou, Fei,et al. 14-Deoxygarcinol improves insulin sensitivity in high-fat diet-induced obese mice via mitigating NF-kappa B/Sirtuin 2-NLRP3-mediated adipose tissue remodeling[J]. ACTA PHARMACOLOGICA SINICA,2022:12.
APA Chen, Jia-li.,Feng, Zhe-ling.,Zhou, Fei.,Lou, Ruo-han.,Peng, Cheng.,...&Lin, Li-gen.(2022).14-Deoxygarcinol improves insulin sensitivity in high-fat diet-induced obese mice via mitigating NF-kappa B/Sirtuin 2-NLRP3-mediated adipose tissue remodeling.ACTA PHARMACOLOGICA SINICA,12.
MLA Chen, Jia-li,et al."14-Deoxygarcinol improves insulin sensitivity in high-fat diet-induced obese mice via mitigating NF-kappa B/Sirtuin 2-NLRP3-mediated adipose tissue remodeling".ACTA PHARMACOLOGICA SINICA (2022):12.

入库方式： OAI收割

来源：上海药物研究所

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