Department of Formula Sciences, College of Oriental Medicine, Dongeui University, Busan 614-052.
Pharm Biol. 2012 Apr;50(4):506-15. doi: 10.3109/13880209.2011.618502. Epub 2011 Dec 1.
Since AMP-activated protein kinase (AMPK) activation in skeletal muscle of obese rodents stimulates fatty acid oxidation, it is reasonable to hypothesize that pharmacological activation of AMPK might be of therapeutic benefit in obesity.
To investigate the effects of the traditional Korean anti-obesity drug GGEx18, a mixture of three herbs, Laminaria japonica Aresch (Laminariaceae), Rheum palmatum L. (Polygonaceae), and Ephedra sinica Stapf (Ephedraceae), on obesity and the involvement of AMPK in this process.
After high fat diet-induced obese mice were treated with GGEx18, we studied the effects of GGEx18 on body weight, fat mass, skeletal muscle lipid accumulation, and the expressions of AMPK, peroxisome proliferator-activated receptor ά (PPARα), and PPARα target genes. The effects of GGEx18 and/or the AMPK inhibitor compound C on lipid accumulation and expression of the above genes were measured in C2C12 skeletal muscle cells.
Administration of GGEx18 to obese mice for 9 weeks significantly (p < 0.05) decreased body and adipose tissue weights compared with obese control mice (p < 0.05). Lipid accumulation in skeletal muscle was inhibited by GGEx18. GGEx18 significantly (p < 0.05) increased skeletal muscle mRNA levels of AMPKα1 and AMPKα2 as well as PPARα and its target genes. Consistent with the in vivo data, GGEx18 inhibited lipid accumulation, and similar activation of genes was observed in GGEx18-treated C2C12 cells. However, compound C inhibited these effects in C2C12 cells.
These results suggest that GGEx18 improves obesity through skeletal muscle AMPK and AMPK-stimulated expression of PPARα and its target enzymes for fatty acid oxidation.
AMP 激活的蛋白激酶（AMPK）在肥胖啮齿动物骨骼肌中的激活刺激脂肪酸氧化，因此可以合理地假设，AMPK 的药理学激活可能对肥胖症具有治疗益处。
研究传统的韩国减肥药 GGEx18（三种草药的混合物，包括海带（Laminariaceae）、大黄（Polygonaceae）和麻黄（Ephedraceae））对肥胖的影响，以及 AMPK 在这一过程中的作用。
在高脂肪饮食诱导肥胖的小鼠接受 GGEx18 治疗后，我们研究了 GGEx18 对体重、脂肪量、骨骼肌脂质积累以及 AMPK、过氧化物酶体增殖物激活受体-α（PPARα）和 PPARα 靶基因表达的影响。在 C2C12 骨骼肌细胞中，测量了 GGEx18 和/或 AMPK 抑制剂化合物 C 对脂质积累和上述基因表达的影响。
给予肥胖小鼠 GGEx18 治疗 9 周，与肥胖对照组相比，体重和脂肪组织重量明显（p<0.05）降低。骨骼肌中的脂质积累被 GGEx18 抑制。GGEx18 显著（p<0.05）增加了骨骼肌中 AMPKα1 和 AMPKα2 以及 PPARα 和其靶基因的 mRNA 水平。与体内数据一致，GGEx18 抑制了 C2C12 细胞中的脂质积累，并且观察到类似的基因激活。然而，化合物 C 在 C2C12 细胞中抑制了这些作用。
这些结果表明，通过骨骼肌 AMPK 和 AMPK 刺激的 PPARα 及其靶酶的表达，GGEx18 改善了肥胖症。
