title: α-Terpineol induces fatty liver in mice mediated by the AMP-activated kinase and sterol response element binding protein pathway.
abstract: The use of herbal medicines in disease prevention and treatment is growing rapidly worldwide, without careful consideration of safety issues. α-Terpineol is a monoterpene alcoholic component of Melaleuca alternifolia, Salvia officinalis and Carthamus tinctorius that is used widely as a flavor and essential oil in food. The present study showed that α-terpineol induces fatty liver via the AMP-activated protein kinase (AMPK)-mTOR-sterol regulatory element-binding protein-1 (SREBP-1) pathway. α-Terpineol-treated hepatocytes had significantly increased neutral lipid accumulation. α-Terpineol suppressed AMPK phosphorylation, and increased p70S6 kinase (p70S6K) phosphorylation and SREBP-1 activation. It also increased luciferase activity in cells transfected with LXRE-tk-Luc and SRE-tk-Luc. Inhibition of mTOR signaling by co-treatment with rapamycin or co-transfection with dominant negative p70S6K blocked completely the effects of α-terpineol. α-Terpineol oral administration to mice for 2weeks led to decreased AMPK phosphorylation and increased SREBP-1 activation in the liver, followed by hepatic lipid accumulation. Conversely, rapamycin co-treatment reversed α-terpineol-induced SREBP-1 activation and fatty liver in mice. These data provide evidence that α-terpineol causes fatty liver, an effect mediated by the AMPK/mTOR/SREBP-1 pathway.
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: You-Jin
authors.initials: YJ
authors.lastname: Choi
authors.forename: Woo-Cheol
authors.initials: WC
authors.lastname: Sim
authors.forename: Hyun Kyu
authors.initials: HK
authors.lastname: Choi
authors.forename: Seung-Ho
authors.initials: SH
authors.lastname: Lee
authors.forename: Byung-Hoon
authors.initials: BH
authors.lastname: Lee
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000502:physiology*; D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D000081005:Cyclohexane Monoterpenes; D053138:Cyclohexenes / Q000633:toxicity*; D017931:DNA Primers; D005234:Fatty Liver / Q000139:chemically induced*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D039821:Monoterpenes / Q000633:toxicity*; D010766:Phosphorylation; D020123:Sirolimus / Q000494:pharmacology; D051780:Sterol Regulatory Element Binding Protein 1 / Q000502:physiology*
chemical_list: D000081005:Cyclohexane Monoterpenes; D053138:Cyclohexenes; D017931:DNA Primers; D039821:Monoterpenes; C497388:Srebf1 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1; C016775:alpha-terpineol; D055372:AMP-Activated Protein Kinases; D020123:Sirolimus