title: 18β-Glycyrrhetinic acid inhibits adipogenic differentiation and stimulates lipolysis.
abstract: 18β-Glycyrrhetinic acid (18β-GA) obtained from the herb liquorice has various pharmacological properties including anti-inflammatory and anti-bacterial activities. However, potential biological anti-obesity activities are unclear. In this study, novel biological activities of 18β-GA in the adipogenesis of 3T3-L1 preadipocytes and in lipolysis of differentiated adipocytes were identified. Mouse 3T3-L1 cells were used as an in vitro model of adipogenesis and lipolysis, using a mixture of insulin/dexamethasone/3-isobutyl-1-methylxanthine (IBMX) to induce differentiation. The amount of lipid droplet accumulation was determined by an AdipoRed assay. The expression of several adipogenic transcription factors and enzymes was investigated using real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blotting. 18β-GA dose-dependently (1-40 μM) significantly decreased lipid accumulation in maturing preadipocytes. In 3T3-L1 preadipocytes, 10 μM of 18β-GA down-regulated the transcriptional levels of the peroxisome proliferator-activated receptor γ, CCAAT/enhancer-binding protein α and adiponectin, which are markers of adipogenic differentiation via Akt phosphorylation. Also, in differentiated adipocytes, 18β-GA increased the level of glycerol release and up-regulated the mRNA of hormone-sensitive lipase, adipose TG lipase and perilipin, as well as the phosphorylation of hormone-sensitive lipase at Serine 563. The results indicate that 18β-GA alters fat mass by directly affecting adipogenesis in maturing preadipocytes and lipolysis in matured adipocytes. Thus, 18β-GA may be useful for the treatment of obesity.
authors.affiliation: Center for Healthcare Technology Development, Biosafety Research Institute, College of Veterinary Medicine, Chonbuk National University, Jeonju, Jeonbuk 561-756, South Korea.
authors.forename: Myung-Hee
authors.initials: MH
authors.lastname: Moon
authors.forename: Jae-Kyo
authors.initials: JK
authors.lastname: Jeong
authors.forename: You-Jin
authors.initials: YJ
authors.lastname: Lee
authors.forename: Jae-Won
authors.initials: JW
authors.lastname: Seol
authors.forename: Dong-Choon
authors.initials: DC
authors.lastname: Ahn
authors.forename: In-Shik
authors.initials: IS
authors.lastname: Kim
authors.forename: Sang-Youel
authors.initials: SY
authors.lastname: Park
mesh_terms: D041721:3T3-L1 Cells; D050156:Adipogenesis / Q000187:drug effects*; D000818:Animals; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins / Q000096:biosynthesis; D015536:Down-Regulation; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D008049:Lipase / Q000378:metabolism; D008066:Lipolysis / Q000187:drug effects*; D051379:Mice; D000070778:Perilipin-1; D010750:Phosphoproteins / Q000096:biosynthesis; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D002787:Sterol Esterase / Q000096:biosynthesis; D015854:Up-Regulation; D000217:Acyltransferases
chemical_list: D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D006034:Glycyrrhetinic Acid; D036341:Intercellular Signaling Peptides and Proteins; D008049:Lipase; D000070778:Perilipin-1; D010750:Phosphoproteins; D051057:Proto-Oncogene Proteins c-akt; D002787:Sterol Esterase; C512925:Dlk1 protein, mouse; C119129:18alpha-glycyrrhetinic acid; C494445:PNPLA2 protein, mouse; D000217:Acyltransferases