Abstract
This study is the first to demonstrate that shizukaol D, a natural compound isolated from Chloranthusjaponicus, can activate AMP- activated protein kinase (AMPK), a key sensor and regulator of intracellular energy metabolism, leading to a decrease in triglyceride and cholesterol levels in HepG2 cells. Furthermore, we found that shizukaol D induces mitochondrial dysfunction by depolarizing the mitochondrial membrane and suppressing energy production, which may result in AMPK activation. Our results provide a possible link between mitochondrial dysfunction and AMPK activation and suggest that shizukaol D might be used to treat metabolic syndrome.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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AMP-Activated Protein Kinases / metabolism*
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Acetyl-CoA Carboxylase / metabolism
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Adenosine Monophosphate / metabolism
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Adenosine Triphosphate / metabolism
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Cell Respiration / drug effects
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Enzyme Activation / drug effects
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Hep G2 Cells
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Humans
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Lipid Metabolism / drug effects*
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Liver / cytology*
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Membrane Potential, Mitochondrial / drug effects
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Mitochondria / drug effects*
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Mitochondria / metabolism*
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Phosphorylation / drug effects
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Plant Extracts / isolation & purification
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Plant Extracts / pharmacology*
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Signal Transduction / drug effects
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Tracheophyta / chemistry*
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Triterpenes / isolation & purification
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Triterpenes / pharmacology*
Substances
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Plant Extracts
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Triterpenes
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shizukaol D
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Adenosine Monophosphate
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Adenosine Triphosphate
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AMP-Activated Protein Kinases
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Acetyl-CoA Carboxylase
Grants and funding
This work was supported in part by grants from Ministry of Science and Technology (#2010CB912102, 2011CB910200), a grant from the National Natural Science Foundation of China (#31130034) (to JRW); and a grant from the Knowledge Innovation Program of the Chinese Academy of Sciences (KSCX2-EW-Q-10) (to HL). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.