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Ajoene, A Stable Garlic By-Product, Inhibits High Fat Diet-Induced Hepatic Steatosis and Oxidative Injury Through LKB1-Dependent AMPK Activation

Title
Ajoene, A Stable Garlic By-Product, Inhibits High Fat Diet-Induced Hepatic Steatosis and Oxidative Injury Through LKB1-Dependent AMPK Activation
Author
황세진
Keywords
LIVER-X-RECEPTOR; ELEMENT-BINDING PROTEIN-1C; NITRIC-OXIDE SYNTHASE; S6 KINASE-1 PATHWAY; INSULIN-RESISTANCE; LIPID-METABOLISM; HEPG2 CELLS; LXR-ALPHA; STRESS; MICE
Issue Date
2011-01
Publisher
MARY ANN LIEBERT INC, 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
Citation
Antioxidants & redox signaling v.14 no.2,2011년, pp.187 - 202
Abstract
Hepatic steatosis, a hepatic component of metabolic syndrome, is common and may progress to steatohepatitis and cirrhosis. The liver X receptor-alpha (LXR alpha)-sterol regulatory element binding protein-1c (SREBP-1c) pathway plays a key role in hepatic steatosis. This study investigated the potential of ajoene, a stable garlic by-product, to inhibit high fat diet (HFD)-induced hepatic steatosis and the underlying mechanism. Ajoene treatment attenuated fat accumulation and induction of lipogenic genes in the liver of HFD-fed mice. Blood biochemical analyses and histopathologic examinations showed that ajoene prevented liver injury with the inhibition of oxidative stress, as evidenced by thiobarbituric acid reactive substances formation and nitrotyrosinylation. Moreover, ajoene treatment inhibited LXR alpha agonist (T0901317)-mediated SREBP-1c activation, and transactivation of the lipogenic target genes in hepatocytes. Ajoene was found to activate AMP-activated protein kinase (AMPK) via LKB1, responsible for the inhibition of p70 ribosomal S6 kinase-1 (S6K1). The ability of ajoene to repress T0901317-induced SREBP-1c expression was antagonized by inhibition of AMPK or activation of S6K1, supporting the role of these kinases in the antisteatotic effect. Our results demonstrate that ajoene has an effect of activating AMPK through LKB1 and inhibit S6K1 activity, contributing to the prevention of SREBP-1c-mediated hepatic lipogenesis via the inhibition of LXR alpha activity. Antioxid Redox Signal. 14, 187-202.
URI
http://online.liebertpub.com/doi/abs/10.1089/ars.2010.3190http://hdl.handle.net/20.500.11754/66205
ISSN
1523-0864; 1557-7716
DOI
10.1089/ars.2010.3190
Appears in Collections:
COLLEGE OF MEDICINE[S](의과대학) > MEDICINE(의학과) > Articles
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