Awazawa Motoharu, Ueki Kohjiro, Inabe Kazunori, Yamauchi Toshimasa, Kaneko Kazuma, Okazaki Yukiko, Bardeesy Nabeel, Ohnishi Shin, Nagai Ryozo, Kadowaki Takashi
Department of Metabolic Diseases, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
Biochem Biophys Res Commun. 2009 Apr 24;382(1):51-6. doi: 10.1016/j.bbrc.2009.02.131. Epub 2009 Feb 28.
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) 1c, the master regulator which controls and upregulates the enzymes involved in fatty acid synthesis, in the liver of +Lepr(db)/+Lepr(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.
脂联素是一种具有胰岛素增敏作用的脂肪因子，已被证明可激活肝脏和骨骼肌中的脂肪酸氧化，从而维持胰岛素敏感性。然而，脂联素在脂肪酸合成中的具体作用尚不清楚。在此我们表明，给予脂联素可急性抑制 +Lepr(db)/+Lepr(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）1c的表达，SREBP 1c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，脂联素通过其功能性受体之一AdipoR1抑制SREBP1c，此外，通过其上游激酶LKB1缺失抑制AMP激活的蛋白激酶（AMPK）可消除脂联素对SREBP1c表达的负面影响。这些数据表明脂联素通过AdipoR1/LKB1/AMPK途径抑制SREBP1c，并提示脂联素在肝脏脂肪酸合成调节中可能发挥作用。
