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.