We investigated the hypotriglyceridemic mechanism of action of linalool, an aromatic monoterpene present in teas and fragrant herbs. Reporter gene and time-resolved fl uorescence resonance energy transfer assays demonstrated that linalool is a direct ligand of PPAR α . Linalool stimulation reduced cellular lipid accumulation regulating PPAR - responsive genes and signifi cantly induced FA oxidation, and its effects were markedly attenuated by silencing PPAR expression. In mice, the oral administration of linalool for 3 weeks reduced plasma TG concentrations in Western-dietfed C57BL/6J mice (31%, P < 0.05) and human apo E2 mice (50%, P < 0.05) and regulated hepatic PPAR α target genes. However, no such effects were seen in PPAR α -defi cient mice. Transcriptome profi ling revealed that linalool stimulation rewired global gene expression in lipid-loaded hepatocytes and that the effects of 1 mM linalool were comparable to those of 0.1 mM fenofi brate. Metabolomic analysis of the mouse plasma revealed that the global metabolite profi les were signifi cantly distinguishable between linalool-fed mice and controls. Notably, the concentrations of saturated FAs were signifi cantly reduced in linalool-fed mice. These fi ndings suggest that the appropriate intake of a natural aromatic compound could exert benefi cial metabolic effects by regulating a cellular nutrient sensor.
ASJC Scopus subject areas
- Cell Biology