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Glycyrrhizic acid suppresses early stage of adipogenesis through repression of MEK/ERK-mediated C/EBPβ and C/EBPδ expression in 3T3-L1 cells.

Abstract
Glycyrrhizic acid (GA), a major constituent of the root of licorice (Glycyrrhiza glabra), and has various biological activities, including anti-obesity property. However, the molecular mechanism of anti-adipogenic effect of GA is still unclear. In this study, we investigated the anti-adipogenic effects of GA in mouse adipocytic 3T3-L1 cells and elucidated its underlying molecular mechanism. GA decreased the intracellular triglyceride level. The expression levels of the adipogenic and lipogenic genes were lowered by treatment with GA in a concertation-dependent manner. In contrast, GA did not affect the lipolytic gene expression and the released glycerol level. GA suppressed the early stage of adipogenesis when it was added for 0-3 h after initiation of adipogenesis. Moreover, GA reduced the mRNA levels of CCAAT/enhancer binding protein (C/EBP) β and C/EBPδ, both of which activate the early stage of adipogenesis. Furthermore, GA decreased phosphorylation of extracellular signal-regulated kinase [ERK: p44/42 mitogen-activated protein kinase (MAPK)] in the early stage of adipogenesis. In addition, a MAPK kinase (MEK) inhibitor, PD98059 reduced the C/EBPβ and C/EBPδ gene expression. These results indicate that GA suppressed the early stage of adipogenesis through repressing the MEK/ERK-mediated C/EBPβ and C/EBPδ expression in 3T3-L1 cells. Thus, GA has an anti-adipogenic ability and a possible agent for treatment of obesity.
AuthorsMasayuki Yamamoto, Yasuna Nagasawa, Ko Fujimori
JournalChemico-biological interactions (Chem Biol Interact) Vol. 346 Pg. 109595 (Sep 01 2021) ISSN: 1872-7786 [Electronic] Ireland
PMID34302803 (Publication Type: Journal Article)
CopyrightCopyright © 2021 Elsevier B.V. All rights reserved.
Chemical References
  • CCAAT-Enhancer-Binding Protein-beta
  • Flavonoids
  • Glucose Transporter Type 4
  • PPAR gamma
  • Slc2a4 protein, mouse
  • Triglycerides
  • CCAAT-Enhancer-Binding Protein-delta
  • Glycyrrhizic Acid
  • Extracellular Signal-Regulated MAP Kinases
  • Mitogen-Activated Protein Kinase Kinases
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
Topics
  • 3T3-L1 Cells
  • Adipogenesis (drug effects)
  • Animals
  • CCAAT-Enhancer-Binding Protein-beta (genetics, metabolism)
  • CCAAT-Enhancer-Binding Protein-delta (genetics, metabolism)
  • Cell Differentiation (drug effects)
  • Cell Survival (drug effects)
  • Down-Regulation (drug effects)
  • Extracellular Signal-Regulated MAP Kinases (metabolism)
  • Flavonoids (pharmacology)
  • Glucose Transporter Type 4 (metabolism)
  • Glycyrrhizic Acid (pharmacology)
  • Lipolysis (drug effects)
  • Mice
  • Mitogen-Activated Protein Kinase Kinases (antagonists & inhibitors, metabolism)
  • PPAR gamma (metabolism)
  • Phosphorylation (drug effects)
  • Triglycerides (metabolism)

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