alpha-Terpineol induces fatty liver in mice mediated by the AMP-activated kinase and sterol response element binding protein pathway

作者：Choi You Jin; Sim Woo Cheol; Choi Hyun Kyu; Lee Seung Ho; Lee Byung Hoon^*

来源：Food and Chemical Toxicology, 2013, 55: 129-136.

DOI：10.1016/j.fct.2012.12.025

• alpha-Terpineol
• SREBP
• AMPK
• mTOR
• p70S6 kinase
• Fatty liver

The use of herbal medicines in disease prevention and treatment is growing rapidly worldwide, without careful consideration of safety issues. alpha-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 alpha-terpineol induces fatty liver via the AMP-activated protein kinase (AMPK)-mTOR-sterol regulatory element-binding protein-1 (SREBP-1) pathway. alpha-Terpineol-treated hepatocytes had significantly increased neutral lipid accumulation. alpha-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 alpha-terpineol. alpha-Terpineol oral administration to mice for 2 weeks led to decreased AMPK phosphorylation and increased SREBP-1 activation in the liver, followed by hepatic lipid accumulation. Conversely, rapamycin co-treatment reversed alpha-terpineol-induced SREBP-1 activation and fatty liver in mice. These data provide evidence that alpha-terpineol causes fatty liver, an effect mediated by the AMPK/mTOR/SREBP-1 pathway. 0 2013 Elsevier Ltd.

• 出版日期2013-5