title: trans-Caryophyllene is a natural agonistic ligand for peroxisome proliferator-activated receptor-α.
abstract: 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)-α through direct interaction with the ligand-binding domain of PPAR-α. 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-α 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-α, the effects of trans-caryophyllene on PPAR-α responsive gene expressions, intracellular triglyceride, fatty acid uptake and oxidation were disappeared. These results indicate that the aroma compound, trans-caryophyllene, is PPAR-α agonist thus regulates cellular lipid metabolism in PPAR-α dependent manners.
authors.affiliation: Department of Biotechnology, Graduate School of Life Sciences and Biotechnology, BK21-PLUS, Korea University, Seoul 136-713, Republic of Korea.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Wu
authors.affiliation: Department of Biotechnology, Graduate School of Life Sciences and Biotechnology, BK21-PLUS, Korea University, Seoul 136-713, Republic of Korea.
authors.forename: Yaoyao
authors.initials: Y
authors.lastname: Jia
authors.affiliation: Department of Biotechnology, Graduate School of Life Sciences and Biotechnology, BK21-PLUS, Korea University, Seoul 136-713, Republic of Korea.
authors.forename: Ji Hae
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Laboratory of Nutrient Sensing and Adipocyte Signaling, Pennington Biomedical Research Center, 6400 Perkins Road, Baton Rouge, LA 70808, USA.
authors.forename: Hee-jin
authors.initials: HJ
authors.lastname: Jun
authors.affiliation: Department of Food and Nutrition, Eulji University, Sujung-Gu, Sungnam, Kyounggi-do 461-713, Republic of Korea.
authors.forename: Hae-Seung
authors.initials: HS
authors.lastname: Lee
authors.affiliation: Department of Biosystems and Biotechnology, Graduate School of Life Sciences and Biotechnology, Korea University, Seoul 136-713, Republic of Korea.
authors.forename: Kwang-Yeon
authors.initials: KY
authors.lastname: Hwang
authors.affiliation: Department of Biotechnology, Graduate School of Life Sciences and Biotechnology, BK21-PLUS, Korea University, Seoul 136-713, Republic of Korea. Electronic address: junelee@korea.ac.kr.
authors.forename: Sung-Joon
authors.initials: SJ
authors.lastname: Lee
mesh_terms: D004305:Dose-Response Relationship, Drug; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D047493:PPAR alpha / Q000819:agonists*; D000081223:Polycyclic Sesquiterpenes; D012717:Sesquiterpenes / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D008024:Ligands; D047493:PPAR alpha; D000081223:Polycyclic Sesquiterpenes; D012717:Sesquiterpenes; C024714:caryophyllene
keywords: Hepatocyte; Lipid metabolism; PPAR-α; trans-Caryophyllene