meso-Dihydroguaiaretic Acid Inhibits Hepatic Lipid Accumulation by Activating AMP-Activated Protein Kinase in Human HepG2 Cells

  • Lee Myoung-Su
    Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University
  • Kim Kyung Jin
    Department of Biomaterials Science and Engineering, Yonsei University
  • Kim Daeyoung
    Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University
  • Lee Kyung-Eun
    Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University
  • Hwang Jae-Kwan
    Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University Department of Biomaterials Science and Engineering, Yonsei University Translational Research Center for Protein Function Control, Yonsei University

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Hepatic lipid accumulation is a major risk factor for dyslipidemia, nonalcoholic fatty liver disease, and insulin resistance. The present study was conducted to evaluate hypolipidemic effects of meso-dihydroguaiaretic acid (MDA), anti-oxidative and anti-inflammatory compound isolated from the Myristica fragrans HOUTT., by oil red O staining, reverse transcription-polymerase chain reaction (RT-PCR), and Western blot. MDA significantly inhibited insulin-induced hepatic lipid accumulation in a dose-dependent manner. The lipid-lowering effect of MDA was accompanied by increased expression of proteins involved in fatty acid oxidation and decreased expression of lipid synthetic proteins. In addition, MDA activated AMP-activated protein kinase (AMPK) as determined by phosphorylation of acetyl-CoA carboxylase (ACC), a downstream target of AMPK. The effects of MDA on lipogenic protein expression were suppressed by pretreatment with compound C, an AMPK inhibitor. Taken together, these findings show that MDA inhibits insulin-induced lipid accumulation in human HepG2 cells by suppressing expression of lipogenic proteins through AMPK signaling, suggesting a potent lipid-lowering agent.

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