Knowledge Management System of Shanghai Institute of Materia Medica, CAS
| 14-Deoxygarcinol improves insulin sensitivity in high-fat diet-induced obese mice via mitigating NF-κB/Sirtuin 2-NLRP3-mediated adipose tissue remodeling | |
Chen Jiali1; Feng Zheling1; Zhou Fei1; Lou Ruohan1; Peng Cheng2; Ye Yang3 ; Lin Ligen1
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| 2023 | |
| Source Publication | ACTA PHARMACOLOGICA SINICA (IF:3.562[JCR-2017],3.773[5-Year]) |
| ISSN | 1671-4083 |
| Volume | 44Issue:2Pages:434 |
| Abstract | Interleukin (IL)-1β is a culprit of adipose tissue inflammation, which in turn causes systematic inflammation and insulin resistance in obese individuals. IL-1β is mainly produced in monocytes and macrophages and marginally in adipocytes, through cleavage of the inactive pro-IL-1β precursor by caspase-1, which is activated via the NLRP3 inflammasome complex. The nuclear factor-κB (NF-κB) 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 THP-1 macrophages, DOG (1.25, 2.5, 5 μM) dose-dependently suppressed the activation of NLRP3 inflammasome and NF-κB 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-1β secretion. Moreover, DOG (1.25, 2.5, 5 μM) 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. |
| Keyword | 14-deoxygarcinol adipose tissue inflammation insulin resistance interleukin-1β NLRP3 inflammasome Sirtuin 2 |
| Language | 英语 |
| Document Type | 期刊论文 |
| Identifier | http://119.78.100.183/handle/2S10ELR8/304783 |
| Collection | 中国科学院上海药物研究所 |
| Affiliation | 1.澳门大学 2.成都中医药大学 3.中国科学院上海药物研究所 |
| Recommended Citation GB/T 7714 | Chen Jiali,Feng Zheling,Zhou Fei,et al. 14-Deoxygarcinol improves insulin sensitivity in high-fat diet-induced obese mice via mitigating NF-κB/Sirtuin 2-NLRP3-mediated adipose tissue remodeling[J]. ACTA PHARMACOLOGICA SINICA,2023,44(2):434. |
| APA | Chen Jiali.,Feng Zheling.,Zhou Fei.,Lou Ruohan.,Peng Cheng.,...&Lin Ligen.(2023).14-Deoxygarcinol improves insulin sensitivity in high-fat diet-induced obese mice via mitigating NF-κB/Sirtuin 2-NLRP3-mediated adipose tissue remodeling.ACTA PHARMACOLOGICA SINICA,44(2),434. |
| MLA | Chen Jiali,et al."14-Deoxygarcinol improves insulin sensitivity in high-fat diet-induced obese mice via mitigating NF-κB/Sirtuin 2-NLRP3-mediated adipose tissue remodeling".ACTA PHARMACOLOGICA SINICA 44.2(2023):434. |
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