Institute for Pharmacology and Toxicology, Biomedical Center, University of Bonn, Bonn, Germany.
Sci Signal. 2009 Dec 1;2(99):ra78. doi: 10.1126/scisignal.2000511.
Brown adipose tissue (BAT) is a primary site of energy expenditure through thermogenesis, which is mediated by the uncoupling protein-1 (UCP-1) in mitochondria. Here, we show that protein kinase G (PKG) is essential for brown fat cell differentiation. Induction of adipogenic markers and fat storage was impaired in the absence of PKGI. Furthermore, PKGI mediated the ability of nitric oxide (NO) and guanosine 3',5'-monophosphate (cGMP) to induce mitochondrial biogenesis and increase the abundance of UCP-1. Mechanistically, we found that PKGI controlled insulin signaling in BAT by inhibiting the activity of RhoA and Rho-associated kinase (ROCK), thereby relieving the inhibitory effects of ROCK on insulin receptor substrate-1 and activating the downstream phosphoinositide 3-kinase-Akt cascade. Thus, PKGI links NO and cGMP signaling with the RhoA-ROCK and the insulin pathways, thereby controlling induction of adipogenic and thermogenic programs during brown fat cell differentiation.
棕色脂肪组织 (BAT) 是通过产热来消耗能量的主要场所，这是由线粒体中的解偶联蛋白 1 (UCP-1) 介导的。在这里，我们表明蛋白激酶 G (PKG) 对棕色脂肪细胞分化至关重要。在缺乏 PKGI 的情况下，诱导脂肪生成标记物和脂肪储存的能力受损。此外，PKGI 介导了一氧化氮 (NO) 和鸟苷 3',5'-环磷酸 (cGMP) 诱导线粒体生物发生和增加 UCP-1 丰度的能力。从机制上讲，我们发现 PKGI 通过抑制 RhoA 和 Rho 相关激酶 (ROCK) 的活性来控制 BAT 中的胰岛素信号，从而减轻 ROCK 对胰岛素受体底物-1 的抑制作用，并激活下游磷酸肌醇 3-激酶-Akt 级联反应。因此，PKGI 将 NO 和 cGMP 信号与 RhoA-ROCK 和胰岛素途径联系起来，从而控制棕色脂肪细胞分化过程中脂肪生成和产热程序的诱导。
