title: Linalool reduces the expression of 3-hydroxy-3-methylglutaryl CoA reductase via sterol regulatory element binding protein-2- and ubiquitin-dependent mechanisms.
abstract: We investigated hypocholesterolemic mechanisms of linalool, an aromatic anti-oxidative monoterpene, which is abundant in teas and essential oils. Oral administration of linalool to mice for 6 weeks significantly lowered total and low-density lipoprotein cholesterol concentrations, and HMG-CoA reductase protein expression (-46%; P<0.05) by both transcriptional and posttranscriptional mechanisms. Linalool suppressed the gene expression of HMG-CoA reductase by reducing the binding of SREBP-2 to its promoter, as assessed by qPCR and chromatin immunoprecipitation, and by inducing ubiquitin-dependent proteolysis of the HMG-CoA reductase. These findings suggest that food molecules with a pleasant scent could exert beneficial metabolic effects through multiple mechanisms.
authors.affiliation: Department of Biotechnology, The Graduate School of Biotechnology, Korea University, Seoul, Republic of Korea.
authors.forename: Sung-Yun
authors.initials: SY
authors.lastname: Cho
authors.forename: Hee-jin
authors.initials: HJ
authors.lastname: Jun
authors.forename: Ji Hae
authors.initials: JH
authors.lastname: Lee
authors.forename: Yaoyao
authors.initials: Y
authors.lastname: Jia
authors.forename: Kyoung Heon
authors.initials: KH
authors.lastname: Kim
authors.forename: Sung-Joon
authors.initials: SJ
authors.lastname: Lee
mesh_terms: D000080462:Acyclic Monoterpenes; D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D002784:Cholesterol / Q000097:blood; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects* / Q000235:genetics; D056945:Hep G2 Cells; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000096:biosynthesis* / Q000235:genetics; D007306:Insecticides / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D051379:Mice; D039821:Monoterpenes / Q000494:pharmacology*; D059748:Proteolysis / Q000187:drug effects; D020218:Response Elements; D051782:Sterol Regulatory Element Binding Protein 2 / Q000235:genetics / Q000378:metabolism*; D025801:Ubiquitin / Q000235:genetics / Q000378:metabolism*
chemical_list: D000080462:Acyclic Monoterpenes; D000924:Anticholesteremic Agents; D007306:Insecticides; D008077:Lipoproteins, LDL; D039821:Monoterpenes; C497390:SREBF2 protein, human; C497391:Srebf2 protein, mouse; D051782:Sterol Regulatory Element Binding Protein 2; D025801:Ubiquitin; D002784:Cholesterol; C018584:linalool; D006903:Hydroxymethylglutaryl CoA Reductases