AICAR, an activator of AMPK, inhibits adipogenesis via the WNT/β-catenin pathway in 3T3-L1 adipocytes
AICAR, an activator of AMPK, inhibits adipogenesis via the WNT/β-catenin pathway in 3T3-L1 adipocytes
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DOI：
10.3892/ijmm.2011.674
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发表时间：
2011-07-01
影响因子：
5.4
通讯作者：
Yoon, Yoosik
中科院分区：
文献类型：
--
作者：
Lee, Haeyong;Kang, Ryunhwa;Yoon, Yoosik
已知AMP激活的蛋白激酶（AMPK）感知细胞能量状态并通过其被AMP（低能状态的指示剂）激活来调节各种细胞能量代谢途径。AMPK激活剂5-氨基咪唑-4-甲酰胺-1-β-D-呋喃核糖苷（AICAR）可有效抑制3 T3-L1细胞的脂肪生成。为了阐明其可能的作用机制，在存在或不存在AICAR的情况下，在3 T3-L1细胞的脂肪形成期间分析β-连环蛋白和WNT/β-连环蛋白途径的其他成员的表达水平。发现AICAR显著增强β-连环蛋白表达及其核积聚。转染β-连环蛋白小干扰RNA（siRNA）可显著抑制AICAR对多种基因表达的影响。脂肪形成的主要基因的表达，包括过氧化物酶体增殖物激活受体（PPAR）γ，CCAAT/增强子结合蛋白（C/EPB）α，脂肪酸结合蛋白（FABP）4和脂蛋白脂肪酶（LPL），这都是由AICAR治疗减少，显着恢复在β-连环蛋白siRNA转染的细胞。在WNT/β-catenin通路的成员中，AICAR处理显著上调低密度脂蛋白受体相关蛋白（LRP）6、散乱（DVL）2和DVL 3的表达，而下调AXIN的表达。本研究提供了令人信服的证据表明AICAR通过调节WNT/β-连环蛋白途径抑制脂肪形成。
AMP-activated protein kinase (AMPK) is known to sense the cellular energy state and regulates various cellular energy metabolism pathways through its activation by AMP, an indicator of a low-energy state. 5-Aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR), an activator of AMPK, efficiently inhibited the adipogenesis of 3T3-L1 cells. To elucidate its possible mechanism of action, the expression levels of beta-catenin and other members of the WNT/beta-catenin pathway were analyzed during the adipogenesis of 3T3-L1 cells in the presence or absence of AICAR. It was found that AICAR significantly enhanced beta-catenin expression and its nuclear accumulation. Transfection of beta-catenin small interfering RNA (siRNA) significantly prevented the effects of AICAR on the expression of various genes. The expression of the major genes of adipogenesis including the peroxisome proliferator-activated receptor (PPAR)gamma, the CCAAT/enhancer binding protein (C/EPB)alpha, the fatty acid binding protein (FABP)4 and lipoprotein lipase (LPL), which were all reduced by AICAR treatment, were significantly recovered in beta-catenin siRNA-transfected cells. Among the members of the WNT/beta-catenin pathway, the expression of low density lipoprotein receptor-related protein (LRP)6, dishevelled (DVL)2 and DVL3 were significantly up-regulated by AICAR treatment, whereas the expression of AXIN was down-regulated. The present study provides compelling evidence that AICAR inhibits adipogenesis through the modulation of the WNT/beta-catenin pathway.