Caffeic Acid Phenethyl Ester Inhibits Differentiation to Adipocytes in 3T3-L1 Mouse Fibroblasts

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  • Juman Sachiko
    School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University
  • Yasui Naomi
    School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University
  • Okuda Hiroto
    School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University
  • Ueda Ai
    School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University
  • Negishi Hiroko
    Graduated School of Humanities and Sciences, Nara Women's University
  • Miki Tomohiro
    School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University
  • Ikeda Katsumi
    School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University

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We investigated the inhibitory effect of caffeic acid phenethyl ester (CAPE) on the differentiation of 3T3-L1 mouse fibroblasts to adipocytes. 3T3-L1 cells were differentiated for adipocytes given high glucose Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% fetal bovine serum (FBS), 1 μM dexamethasone (DEX), 500 μM isobutylmethylxanthine (IBMX), and 5 μg/ml insulin for 7 days. After differentiation, cells were stained with Oil-Red-O to detect oil droplets in adipocytes. Additionally, the cells were lysed and measured for triglyceride contents. Total RNA was isolated from differentiated cells on day 0, 4 and 7. Then, RNA was analyzed using reverse transcription (RT)-polymerase chain reaction (PCR). CAPE dose-dependently suppressed oil droplet accumulation and reduced the droplet size. These findings showed that CAPE at concentrations of 25 to 50 μM could significantly inhibit triglyceride deposition (p<0.05). Treatment of 3T3-L1 with CAPE reduced the mRNA levels of peroxisome proliferator-activated receptor (PPAR) gamma and CCAAT/enhancer-binding protein (C/EBPalpha). Fatty acid synthase (Fas) and adipocyte-specific fatty acid binding protein (aP2) are known to be associated with lipid metabolism in adipocytes, and both Fas mRNA and aP2 mRNA were significantly suppressed by CAPE treatment. These findings suggested that CAPE suppresses 3T3-L1 differentiation to adipocytes through inhibition of PPARgamma, C/EBPalpha, Fas and aP2 expression.

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