Nobiletin enhances differentiation and lipolysis of 3T3-L1 adipocytes

Nobiletin enhances differentiation and lipolysis of 3T3-L1 adipocytes
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DOI:
10.1016/j.bbrc.2007.03.169
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发表时间:
2007-06-01
影响因子:
3.1
通讯作者:
Sekiya, Keizo
Sekiya, Keizo
中科院分区:
生物学4区
文献类型:
--
作者:
Saito, Takeshi;Abe, Daigo;Sekiya, Keizo

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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。川陈皮素呈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分析表明,川陈皮素增加了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)的靶标以及PPARγ本身,然而,川陈皮素不表现出PPARγ配体活性。我们观察到川陈皮素可增加CCAAT/增强子结合蛋白β(C/EBPβ)的表达,它是PPARγ的一种转录因子。川陈皮素还增强了在C/EBPβ表达中起重要作用的环磷腺苷酸反应元件结合蛋白(CREB)和细胞外信号调节激酶(ERK)的激活。此外,川陈皮素刺激了分化脂肪细胞中的脂解作用,已知脂解作用可由环磷腺苷酸途径刺激。这些结果表明,川陈皮素通过激活由环磷腺苷酸/CREB介导的信号级联,增强了脂肪细胞的分化和脂解作用。(c)2007爱思唯尔公司。保留所有权利。
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 (PPAR gamma) targets and PPAR gamma itself, however, nobiletin did not exhibit PPAR gamma ligand activity. We observed the expression of CCAAT/enhancer binding protein beta(C/EBP beta), a transcription factor for PPAR gamma, 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/EBP beta 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. (c) 2007 Elsevier Inc. All rights reserved.