Guggulsterone inhibits adipocyte differentiation and induces apoptosis in 3T3-L1 cells

Obesity (Silver Spring). 2008 Jan;16(1):16-22. doi: 10.1038/oby.2007.24.

Abstract

Objective: To determine the effects of guggulsterone (GS), the active substance in guggulipid, on apoptosis, adipogenesis, and lipolysis using 3T3-L1 cells.

Methods and procedures: For apoptosis and lipolysis experiments, mature adipocytes were treated with GS isomers. Viability, apoptosis, and caspase 3/7 activation were quantified using MTS, enzyme-linked immunosorbent assay (ELISA), caspase-Glo 3/7 activity assay, respectively. The expression of cytochrome c was demonstrated by western blot. Lipolysis was quantified by measuring the release of glycerol. For adipogenesis experiments, postconfluent preadipocytes were incubated with GS isomers for up to 6 days during maturation. Adipogenesis was quantified by measuring lipid content using Nile Red dye. Western blot was also used to demonstrate the adipocyte-specific transcription factors peroxisome proliferator-activated receptor gamma2 (PPARgamma2), CCAAT/enhancer binding protein alpha (C/EBPalpha), and C/EBPbeta.

Results: In mature adipocytes cis-GS decreased viability, whereas the trans-GS isomer had little effect. Both isomers caused dose-dependent increases in apoptosis and cis-GS was more effective than trans-GS in inducing apoptosis. cis- and trans-GS also increased caspase-3 activity and release of cytochrome c from mitochondria. In maturing preadipocytes, both isomers were equally effective in reducing lipid content. The adipocyte-specific transcription factors PPARgamma2, C/EBPalpha, and C/EBPbeta were downregulated after treatment with cis-GS during the maturation period. Furthermore, cis-GS increased basal lipolysis of mature adipocytes, but trans-GS had no effect.

Discussion: These results indicate that GS isomers may exert antiobesity effects by inhibiting differentiation of preadipocytes, and by inducing apoptosis and promoting lipolysis of mature adipocytes. The cis-GS isomer was more potent than the trans-GS isomer in inducing apoptosis and lipolysis in mature adipocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / drug effects
  • Adipocytes / metabolism
  • Adipocytes / pathology*
  • Animals
  • Apoptosis / drug effects*
  • Caspase 3 / metabolism
  • Caspase 7 / metabolism
  • Cell Differentiation / drug effects*
  • Cell Survival / drug effects
  • Cytochromes c / metabolism
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Lipolysis / drug effects
  • Mice
  • PPAR gamma / metabolism
  • Phosphorylation / drug effects
  • Pregnenediones / pharmacology*
  • Triglycerides / metabolism

Substances

  • PPAR gamma
  • Pregnenediones
  • Triglycerides
  • Cytochromes c
  • pregna-4,17-diene-3,16-dione
  • Extracellular Signal-Regulated MAP Kinases
  • Caspase 3
  • Caspase 7