Modulation of Lipid Metabolism by Celastrol
Zhang, Ting1,2; Zhao, Qi1,2; Xiao, Xuerong1; Yang, Rui1,2; Hu, Dandan1; Zhu, Xu1,2; Gonzalez, Frank J.3; Li, Fei1,4
2019-03-01
Source PublicationJOURNAL OF PROTEOME RESEARCH
ISSN1535-3893
Volume18Issue:3Pages:1133-1144
AbstractHyperlipidemia, characterized by high serum lipids, is a risk factor for cardiovascular disease. Recent studies have identified an important role for celastrol, a proteasome inhibitor isolated from Tripterygium wilfordii Hook. F., in obesity-related metabolic disorders. However, the exact influences of celastrol on lipid metabolism remain largely unknown. Celastrol inhibited the terminal differentiation of 3T3-L1 adipocytes and decreased the levels of triglycerides in wild-type mice. Lipidomics analysis revealed that celastrol increased the metabolism of lysophosphatidylcholines (LPCs), phosphatidylcholines (PCs), sphingomyelins (SMs), and phosphatidylethanolamines (PEs). Further, celastrol reversed the tyloxapol-induced hyperlipidemia induced associated with increased plasma LPCs, PCs, SMs, and ceramides (CMs). Among these lipids, LPC(16:0), LPC(18:1), PC(22:2/15:0), and SM(d18:1/22:0) were also decreased by celastrol in cultured 3T3-L1 adipocytes, mice, and tyloxapol-treated mice. The mRNAs encoded by hepatic genes associated with lipid synthesis and catabolism, including Lpcat1, Pld1, Smpd3, and Sptc2, were altered in tyloxapol-induced hyperlipidemia, and significantly recovered by celastrol treatment. The effect of celastrol on lipid metabolism was significantly reduced in Fxr-null mice, resulting in decreased Cers6 and Acer2 mRNAs compared to wild-type mice. These results establish that FXR was responsible in part for the effects of celastrol in controlling lipid metabolism and contributing to the recovery of aberrant lipid metabolism in obesity-related metabolic disorders.
Keywordcelastrol lipidomics hyperlipidemia LC-MS
Indexed BySCI
Language英语
Document Type期刊论文
Identifierhttp://ir.kib.ac.cn/handle/151853/65200
Collection植物化学与西部植物资源持续利用国家重点实验室
Corresponding AuthorLi, Fei
Affiliation1.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, Kunming 650201, Yunnan, Peoples R China
2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
3.NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA
4.Jiangxi Univ Tradit Chinese Med, Nanchang 330004, Jiangxi, Peoples R China
Recommended Citation
GB/T 7714
Zhang, Ting,Zhao, Qi,Xiao, Xuerong,et al. Modulation of Lipid Metabolism by Celastrol[J]. JOURNAL OF PROTEOME RESEARCH,2019,18(3):1133-1144.
APA Zhang, Ting.,Zhao, Qi.,Xiao, Xuerong.,Yang, Rui.,Hu, Dandan.,...&Li, Fei.(2019).Modulation of Lipid Metabolism by Celastrol.JOURNAL OF PROTEOME RESEARCH,18(3),1133-1144.
MLA Zhang, Ting,et al."Modulation of Lipid Metabolism by Celastrol".JOURNAL OF PROTEOME RESEARCH 18.3(2019):1133-1144.
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