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

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)-alpha through direct interaction with the ligand-binding domain of PPAR-alpha. 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-alpha 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-alpha the effects of trans-caryophyllene on PPAR-alpha responsive gene expressions, intracellular triglyceride, fatty acid uptake and oxidation were disappeared. These results indicate that the aroma compound, trans-caryophyllene, is PPAR-alpha agonist thus regulates cellular lipid metabolism in PPAR-alpha dependent manners. (C) 2014 Elsevier Ltd. All rights reserved.