Linalool is a PPAR? ligand that reduces plasma TG levels and rewires the hepatic transcriptome and plasma metabolome.

ABSTRACT: We investigated the hypotriglyceridemic mechanism of action of linalool, an aromatic monoterpene present in teas and fragrant herbs. Reporter gene and time-resolved fluorescence resonance energy transfer assays demonstrated that linalool is a direct ligand of PPAR?. Linalool stimulation reduced cellular lipid accumulation regulating PPAR?-responsive genes and significantly 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-diet-fed C57BL/6J mice (31%, P < 0.05) and human apo E2 mice (50%, P < 0.05) and regulated hepatic PPAR? target genes. However, no such effects were seen in PPAR?-deficient mice. Transcriptome profiling 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 fenofibrate. Metabolomic analysis of the mouse plasma revealed that the global metabolite profiles were significantly distinguishable between linalool-fed mice and controls. Notably, the concentrations of saturated FAs were significantly reduced in linalool-fed mice. These findings suggest that the appropriate intake of a natural aromatic compound could exert beneficial metabolic effects by regulating a cellular nutrient sensor.

SUBMITTER: Jun HJ 

PROVIDER: S-EPMC4031941 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature