title: Linalool is a PPARα 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 PPARα. Linalool stimulation reduced cellular lipid accumulation regulating PPARα-responsive genes and significantly induced FA oxidation, and its effects were markedly attenuated by silencing PPARα 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 PPARα target genes. However, no such effects were seen in PPARα-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.
authors.affiliation: Department of Biotechnology, Graduate School of Life Sciences and Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, South Korea.
authors.forename: Hee-Jin
authors.initials: HJ
authors.lastname: Jun
authors.affiliation: Department of Biotechnology, Graduate School of Life Sciences and Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, South Korea.
authors.forename: Ji Hae
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Biotechnology, Graduate School of Life Sciences and Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, South Korea.
authors.forename: Jiyoung
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Biotechnology, Graduate School of Life Sciences and Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, South Korea.
authors.forename: Yaoyao
authors.initials: Y
authors.lastname: Jia
authors.affiliation: Department of Biotechnology, Graduate School of Life Sciences and Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, South Korea.
authors.forename: Kyoung Heon
authors.initials: KH
authors.lastname: Kim
authors.affiliation: Department of Biosystems and Biotechnology, Graduate School of Life Sciences and Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, South Korea.
authors.forename: Kwang Yeon
authors.initials: KY
authors.lastname: Hwang
authors.affiliation: Department of Biotechnology, Graduate School of Life Sciences and Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, South Korea.
authors.forename: Eun Ju
authors.initials: EJ
authors.lastname: Yun
authors.affiliation: Department of Biotechnology, Graduate School of Life Sciences and Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, South Korea.
authors.forename: Kyoung-Rok
authors.initials: KR
authors.lastname: Do
authors.affiliation: Department of Biotechnology, Graduate School of Life Sciences and Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, South Korea.
authors.forename: Sung-Joon
authors.initials: SJ
authors.lastname: Lee
mesh_terms: D000080462:Acyclic Monoterpenes; D000818:Animals; D022781:Hepatocytes / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D055442:Metabolome / Q000187:drug effects*; D051379:Mice; D008817:Mice, Mutant Strains; D039821:Monoterpenes / Q000494:pharmacology*; D047493:PPAR alpha / Q000819:agonists / Q000096:biosynthesis* / Q000235:genetics; D059467:Transcriptome / Q000187:drug effects*; D014280:Triglycerides / Q000097:blood* / Q000235:genetics
chemical_list: D000080462:Acyclic Monoterpenes; D039821:Monoterpenes; D047493:PPAR alpha; D014280:Triglycerides; C018584:linalool
keywords: agonist; linalool; peroxisome proliferator-activated receptor-α; triglyceride
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