Saito Takeshi, Abe Daigo, Sekiya Keizo
National Agricultural Research Center for Western Region, 1-3-1 Senyu-cho, Zentsuji 765-8508, Japan.
Biochem Biophys Res Commun. 2007 Jun 1;357(2):371-6. doi: 10.1016/j.bbrc.2007.03.169. Epub 2007 Apr 5.
Nobiletin is a polymethoxylated flavone found in certain citrus fruits. Here we demonstrate that nobiletin enhance differentiation of 3T3-L1 preadipocytes. Nobiletin dose-dependently increased accumulation of lipid droplets in adipocytes. Quantitative RT-PCR analyses indicated that nobiletin increased the expression of genes critical for acquisition of the adipocyte phenotype. Some of them were known peroxisome proliferator activated receptor gamma (PPARgamma) targets and PPARgamma itself, however, nobiletin did not exhibit PPARgamma ligand activity. We observed the expression of CCAAT/enhancer binding protein beta (C/EBPbeta), a transcription factor for PPARgamma, was increased by nobiletin. The activation of cAMP-responsive element binding protein (CREB) and extracellular signal-regulated kinase (ERK), which play important roles in C/EBPbeta expression were also potentiated by nobiletin. Furthermore, nobiletin stimulated lipolysis in differentiated adipocytes, which is known to be stimulated by cAMP pathway. These results suggested that nobiletin enhanced both differentiation and lipolysis of adipocyte through activation of signaling cascades mediated by cAMP/CREB.
川陈皮素是一种在某些柑橘类水果中发现的多甲氧基黄酮。在此我们证明，川陈皮素可促进3T3-L1前脂肪细胞的分化。川陈皮素能剂量依赖性地增加脂肪细胞中脂滴的积累。定量逆转录聚合酶链反应（RT-PCR）分析表明，川陈皮素可增加对获得脂肪细胞表型至关重要的基因的表达。其中一些是已知的过氧化物酶体增殖物激活受体γ（PPARγ）靶基因以及PPARγ本身，然而，川陈皮素并未表现出PPARγ配体活性。我们观察到，川陈皮素可增加PPARγ的转录因子CCAAT/增强子结合蛋白β（C/EBPβ）的表达。在C/EBPβ表达中起重要作用的环磷酸腺苷反应元件结合蛋白（CREB）和细胞外信号调节激酶（ERK）的激活也被川陈皮素增强。此外，川陈皮素可刺激分化的脂肪细胞中的脂肪分解，已知这是由环磷酸腺苷（cAMP）途径刺激的。这些结果表明，川陈皮素通过激活由cAMP/CREB介导的信号级联反应，增强了脂肪细胞的分化和脂肪分解。
