Trans-Caryophyllene is a natural agonistic ligand for peroxisome proliferator-activated receptor-α

Chunyan Wu; Yaoyao Jia; Ji Hae Lee; Hee Jin Jun; Hae Seung Lee; Kwang Yeon Hwang; Sung Joon Lee

doi:10.1016/j.bmcl.2014.04.112

Trans-Caryophyllene is a natural agonistic ligand for peroxisome proliferator-activated receptor-α

Chunyan Wu
, Yaoyao Jia
, Ji Hae Lee
, Hee Jin Jun
, Hae Seung Lee
, Kwang Yeon Hwang
, Sung Joon Lee^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

49 Citations (Scopus)

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.

Original language	English
Pages (from-to)	3168-3174
Number of pages	7
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	24
Issue number	14
DOIs	https://doi.org/10.1016/j.bmcl.2014.04.112
Publication status	Published - 2014 Jul 15

Bibliographical note

Funding Information:
This work was supported by Basic Science Research Program of the National Research Foundation of Korea (NRF), funded by the Ministry of Education, Science and Technology (No. 2013R1A2A2A01016176 ), and a grant ( 14162MFDS973 ) from Ministry of Food and Drug Safety in 2014. The SPR instrument was provided by the Korea Basic Science Institute . We thank Professor Hyun-Gyu Song for the advice on FRET analysis.

Keywords

Hepatocyte
Lipid metabolism
PPAR-α
trans-Caryophyllene

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/j.bmcl.2014.04.112

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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.",

keywords = "Hepatocyte, Lipid metabolism, PPAR-α, trans-Caryophyllene",

author = "Chunyan Wu and Yaoyao Jia and Lee, \{Ji Hae\} and Jun, \{Hee Jin\} and Lee, \{Hae Seung\} and Hwang, \{Kwang Yeon\} and Lee, \{Sung Joon\}",

note = "Funding Information: This work was supported by Basic Science Research Program of the National Research Foundation of Korea (NRF), funded by the Ministry of Education, Science and Technology (No. 2013R1A2A2A01016176 ), and a grant ( 14162MFDS973 ) from Ministry of Food and Drug Safety in 2014. The SPR instrument was provided by the Korea Basic Science Institute . We thank Professor Hyun-Gyu Song for the advice on FRET analysis. ",

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doi = "10.1016/j.bmcl.2014.04.112",

language = "English",

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journal = "Bioorganic and Medicinal Chemistry Letters",

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AU - Wu, Chunyan

AU - Jia, Yaoyao

AU - Lee, Ji Hae

AU - Jun, Hee Jin

AU - Lee, Hae Seung

AU - Hwang, Kwang Yeon

AU - Lee, Sung Joon

N1 - Funding Information: This work was supported by Basic Science Research Program of the National Research Foundation of Korea (NRF), funded by the Ministry of Education, Science and Technology (No. 2013R1A2A2A01016176 ), and a grant ( 14162MFDS973 ) from Ministry of Food and Drug Safety in 2014. The SPR instrument was provided by the Korea Basic Science Institute . We thank Professor Hyun-Gyu Song for the advice on FRET analysis.

PY - 2014/7/15

Y1 - 2014/7/15

N2 - 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.

AB - 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.

KW - Hepatocyte

KW - Lipid metabolism

KW - PPAR-α

KW - trans-Caryophyllene

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ER -

Trans-Caryophyllene is a natural agonistic ligand for peroxisome proliferator-activated receptor-α

Abstract

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Keywords

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