title: meso-Dihydroguaiaretic acid inhibits hepatic lipid accumulation by activating AMP-activated protein kinase in human HepG2 cells.
abstract: 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.
authors.affiliation: Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 120–749, Korea.
authors.forename: Myoung-Su
authors.initials: MS
authors.lastname: Lee
authors.forename: Kyung Jin
authors.initials: KJ
authors.lastname: Kim
authors.forename: Daeyoung
authors.initials: D
authors.lastname: Kim
authors.forename: Kyung-Eun
authors.initials: KE
authors.lastname: Lee
authors.forename: Jae-Kwan
authors.initials: JK
authors.lastname: Hwang
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D018929:Cell Culture Techniques; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D050171:Dyslipidemias / Q000473:pathology; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005234:Fatty Liver / Q000473:pathology; D006139:Guaiacol / Q000031:analogs & derivatives* / Q000494:pharmacology; D056945:Hep G2 Cells; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D007333:Insulin Resistance / Q000502:physiology; D017705:Lignans / Q000494:pharmacology*; D050356:Lipid Metabolism / Q000187:drug effects / Q000502:physiology; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D058990:Molecular Targeted Therapy; D026323:Myristica; D065626:Non-alcoholic Fatty Liver Disease; D010766:Phosphorylation / Q000187:drug effects; D008517:Phytotherapy; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D000960:Hypolipidemic Agents; D017705:Lignans; D010936:Plant Extracts; D011720:Pyrazoles; D011743:Pyrimidines; C516138:dorsomorphin; C015816:dihydroguaiaretic acid; D006139:Guaiacol; D055372:AMP-Activated Protein Kinases; D000103:Acetyl-CoA Carboxylase