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  • Title: Guggulsterone inhibits adipocyte differentiation and induces apoptosis in 3T3-L1 cells.
    Author: Yang JY, Della-Fera MA, Baile CA.
    Journal: Obesity (Silver Spring); 2008 Jan; 16(1):16-22. PubMed ID: 18223606.
    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.
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