18β-Glycyrrhetinic acid inhibits adipogenic differentiation and stimulates lipolysis

Biochem Biophys Res Commun. 2012 Apr 20;420(4):805-10. doi: 10.1016/j.bbrc.2012.03.078. Epub 2012 Mar 21.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Adipogenesis / drug effects*
  • Animals
  • Calcium-Binding Proteins
  • Carrier Proteins / biosynthesis
  • Down-Regulation
  • Glycyrrhetinic Acid / analogs & derivatives*
  • Glycyrrhetinic Acid / pharmacology
  • Intercellular Signaling Peptides and Proteins / genetics
  • Lipase / metabolism
  • Lipolysis / drug effects*
  • Mice
  • Perilipin-1
  • Phosphoproteins / biosynthesis
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors
  • Proto-Oncogene Proteins c-akt / metabolism
  • Sterol Esterase / biosynthesis
  • Up-Regulation

Substances

  • Calcium-Binding Proteins
  • Carrier Proteins
  • Dlk1 protein, mouse
  • Intercellular Signaling Peptides and Proteins
  • Perilipin-1
  • Phosphoproteins
  • 18alpha-glycyrrhetinic acid
  • Proto-Oncogene Proteins c-akt
  • Sterol Esterase
  • Lipase
  • PNPLA2 protein, mouse
  • Glycyrrhetinic Acid