2. Academic Validation
  3. trans-Caryophyllene is a natural agonistic ligand for peroxisome proliferator-activated receptor-α

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

  • Bioorg Med Chem Lett. 2014 Jul 15;24(14):3168-74. doi: 10.1016/j.bmcl.2014.04.112.
Chunyan Wu 1,  Yaoyao Jia 1,  Ji Hae Lee 1,  Hee-jin Jun 2,  Hae-Seung Lee 3,  Kwang-Yeon Hwang 4,  Sung-Joon Lee 5
Affiliations

Affiliations

  • 1 Department of Biotechnology, Graduate School of Life Sciences and Biotechnology, BK21-PLUS, Korea University, Seoul 136-713, Republic of Korea.
  • 2 Laboratory of Nutrient Sensing and Adipocyte Signaling, Pennington Biomedical Research Center, 6400 Perkins Road, Baton Rouge, LA 70808, USA.
  • 3 Department of Food and Nutrition, Eulji University, Sujung-Gu, Sungnam, Kyounggi-do 461-713, Republic of Korea.
  • 4 Department of Biosystems and Biotechnology, Graduate School of Life Sciences and Biotechnology, Korea University, Seoul 136-713, Republic of Korea.
  • 5 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.
PMID: 24856059 DOI: 10.1016/j.bmcl.2014.04.112
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.

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