title: Licochalcone A regulates hepatic lipid metabolism through activation of AMP-activated protein kinase.
abstract: Licochalcone A (LA) is a major phenolic ingredient of Glycyrrhiza plant. Although multiple pharmacological activities of LA have been reported, effect on hepatic lipid metabolism is unknown yet. The present study showed LA to suppress the hepatic triglyceride accumulation in HepG2 cells and ICR mice fed on a high fat diet (HFD). LA inhibited lipogenesis via suppression of sterol regulatory element-binding protein 1c (SREBP1c) and its target enzymes (stearoyl-CoA desaturase 1, fatty acid synthase and glycerol-3-phosphate acyltransferase) transcription. In addition, LA up-regulated gene expression of proteins such as peroxisome proliferator-activated receptor α (PPARα) and fatty acid transporter (FAT/CD36), which are responsible for lipolysis and fatty acid transport, respectively. These effects were mediated through activation of AMP-activated protein kinase (AMPK), and were abrogated when HepG2 cells were treated with an AMPK inhibitor, compound C. To explore how LA activates AMPK, oxygen consumption rate and ATP levels were measured in HepG2 cells. LA significantly inhibited the mitochondrial respiration and ATP levels, suggesting that LA activated AMPK indirectly. In animal study, LA (5 and 10mg/kg) was orally administered to six-week-old mice once a day for 3 weeks. In vitro results were likely to hold true in vivo experiment, as LA markedly lowered the triglyceride levels and activated AMPK signaling pathway in the liver of ICR mice fed on a HFD. In conclusion, the current study suggests that LA suppressed hepatic triglyceride accumulation through modulation of AMPK-SREBP signaling pathway and thus LA may be a potential therapeutic agent for treating fatty liver disease.
authors.affiliation: Department of Pharmacology and Clinical Pharmacy, College of Pharmacy, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Hai Yan
authors.initials: HY
authors.lastname: Quan
authors.forename: Soo Jung
authors.initials: SJ
authors.lastname: Kim
authors.forename: Do Yeon
authors.initials: DY
authors.lastname: Kim
authors.forename: Hee Kyung
authors.initials: HK
authors.lastname: Jo
authors.forename: Go Woon
authors.initials: GW
authors.lastname: Kim
authors.forename: Sung Hyun
authors.initials: SH
authors.lastname: Chung
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D047188:Chalcones / Q000494:pharmacology*; D059305:Diet, High-Fat; D004041:Dietary Fats / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects*; D015870:Gene Expression / Q000187:drug effects; D006035:Glycyrrhiza / Q000737:chemistry*; D056945:Hep G2 Cells; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects / Q000235:genetics; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D008928:Mitochondria / Q000187:drug effects; D010101:Oxygen Consumption; D010936:Plant Extracts / Q000494:pharmacology*; D015398:Signal Transduction; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism; D014280:Triglycerides / Q000097:blood / Q000378:metabolism*
chemical_list: D047188:Chalcones; D004041:Dietary Fats; D010936:Plant Extracts; D051780:Sterol Regulatory Element Binding Protein 1; D014280:Triglycerides; D000255:Adenosine Triphosphate; D055372:AMP-Activated Protein Kinases; C070840:licochalcone A