trans-Caryophyllene is a natural agonistic ligand for peroxisome proliferator-activated receptor-伪

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• 作者：Chunyan Wu^a ; Yaoyao Jia^a ; Ji Hae Lee^a ; Hee-jin Jun^b ; Hae-Seung Lee^c ; Kwang-Yeon Hwang^d ; Sung-Joon Lee^a ; ^{junelee@korea.ac.kr" class="auth_mail}
• 关键词：PPAR ; peroxisome proliferator-activated receptor ; LBD ; ligand-binding domain ; SPR ; surface plasmon resonance ; TR-FRET ; time-resolved fluorescent resonance energy transfer ; TG ; triglyceride ; HTG ; hypertriglyceridemia ; RXR ; retinoid X receptor ; EO ; essential oils ; LDL ; low-density lipoprotein ; SREBP-1c ; sterol regulatory element binding protein ; HDL ; high-density lipoprotein ; EC50 ; the half maximal effective concentration ; KD ; equilibrium dissociation constant ; FATP4 ; fatty acid transport protein
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：15 July 2014
• 年：2014
• 卷：24
• 期：14
• 页码：3168-3174
• 全文大小：958 K

文摘

Intake of dietary aroma compounds may regulate cellular lipid metabolism. We demonstrated that trans-caryophyllene, a flavor compound in plant foods and teas, activates peroxisome proliferator-activated receptor (PPAR)-伪 through direct interaction with the ligand-binding domain of PPAR-伪. The agonistic activity of trans-caryophyllene was investigated by the luciferase reporter assay, surface plasmon resonance, and time-resolved fluorescence resonance energy transfer assay. Following the stimulation of cells with trans-caryophyllene, intracellular triglyceride concentrations were significantly reduced by 17%, and hepatic fatty acid uptake was significantly increased by 31%. The rate of fatty acid oxidation was also significantly increased. The expressions of PPAR-伪 and its target genes and proteins in fatty acid uptake and oxidation were significantly up-regulated as well. In HepG2 cells transfected with small interfering RNA of PPAR-伪, the effects of trans-caryophyllene on PPAR-伪 responsive gene expressions, intracellular triglyceride, fatty acid uptake and oxidation were disappeared. These results indicate that the aroma compound, trans-caryophyllene, is PPAR-伪 agonist thus regulates cellular lipid metabolism in PPAR-伪 dependent manners.