Adiponectin suppresses hepatic SREBP1c expression in an AdipoR1/LKB1/AMPK dependent pathway
Adiponectin suppresses hepatic SREBP1c expression in an AdipoR1/LKB1/AMPK dependent pathway
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DOI：
10.1016/j.bbrc.2009.02.131
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发表时间：
2009-04-24
影响因子：
3.1
通讯作者：
Kadowaki, Takashi
中科院分区：
文献类型：
--
作者：
Awazawa, Motoharu;Ueki, Kohjiro;Kadowaki, Takashi
脂联素是一种胰岛素增敏性脂肪因子，可激活肝脏和骨骼肌中的脂肪酸氧化，从而维持胰岛素的敏感性。然而，脂联素在脂肪酸合成中的确切作用知之甚少。在此，我们发现脂联素给药可急性抑制+Lepr（db）/+Lep（db）（db/db）小鼠肝脏以及培养的肝细胞中固醇调节元件结合蛋白（SREBP）Ic的表达，该蛋白是控制和上调参与脂肪酸合成的酶的主要调节因子。我们还表明，脂联素抑制SREBP 1c的AdipoR 1，脂联素的功能受体之一，此外，抑制AMP激活的蛋白激酶（AMPK）通过其上游激酶LKB 1删除取消了脂联素对SREBP 1c表达的负面影响。这些数据表明，脂联素通过AdipoR 1/LKB 1/AMPK途径抑制SREBP 1c，并表明脂联素在调节肝脏脂肪酸合成中可能发挥作用。(C)2009爱思唯尔公司All rights reserved.
Adiponectin, one of the insulin-sensitizing adipokines, has been shown to activate fatty acid oxidation in liver and skeletal muscle, thus maintaining insulin sensitivity. However, the precise roles of adiponectin in fatty acid synthesis are poorly understood. Here we show that adiponectin administration acutely suppresses expression of sterol regulatory element-binding protein (SREBP) I c, the master regulator which controls and upregulates the enzymes involved in fatty acid synthesis, in the liver of +Lepr(db)/+Lep(db) (db/db) mouse as well as in Cultured hepatocytes. We also show that adiponectin suppresses SREBP1c by AdipoR1, one of the functional receptors for adiponetin, and furthermore that suppressing either AMP-activated protein kinase (AMPK) via its upstream kinase LKB1 deletion cancels the negative effect of adiponectin on SREBP1c expression. These data show that adiponectin suppresses SREBP1c through the AdipoR1/LKB1/AMPK pathway, and suggest a possible role for adiponectin in the regulation of hepatic fatty acid synthesis. (C) 2009 Elsevier Inc. All rights reserved.