| Autor: |
Sun SM; Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.; University of Chinese Academy of Sciences, Beijing, 100049, China., Xie ZF; Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China., Zhang YM; Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.; University of Chinese Academy of Sciences, Beijing, 100049, China.; Yantai Key Laboratory of Nanomedicine & Advanced Preparations, Yantai Institute of Materia Medica, Yantai, 264000, China., Zhang XW; Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China., Zhou CD; Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China., Yin JP; Yantai Key Laboratory of Nanomedicine & Advanced Preparations, Yantai Institute of Materia Medica, Yantai, 264000, China., Yu YY; Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China., Cui SC; Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China., Jiang HW; Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China., Li TT; Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.; University of Chinese Academy of Sciences, Beijing, 100049, China.; School of Life Science and Technology, ShanghaiTech University, Shanghai, 201210, China., Li J; Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.; University of Chinese Academy of Sciences, Beijing, 100049, China.; School of Life Science and Technology, ShanghaiTech University, Shanghai, 201210, China., Nan FJ; Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China. fjnan@simm.ac.cn.; University of Chinese Academy of Sciences, Beijing, 100049, China. fjnan@simm.ac.cn.; Yantai Key Laboratory of Nanomedicine & Advanced Preparations, Yantai Institute of Materia Medica, Yantai, 264000, China. fjnan@simm.ac.cn., Li JY; Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China. jyli@simm.ac.cn.; University of Chinese Academy of Sciences, Beijing, 100049, China. jyli@simm.ac.cn. |
| Abstrakt: |
Dyslipidemia is a chronic metabolic disease characterized by elevated levels of lipids in plasma. Recently, various studies demonstrate that the increased activity of adenosine 5'-monophosphate-activated protein kinase (AMPK) causes health benefits in energy regulation. Thus, great efforts have been made to develop AMPK activators as a metabolic syndrome treatment. In the present study, we investigated the effects of the AMPK activator C24 on dyslipidemia and the potential mechanisms. We showed that C24 (5-40 μM) dose-dependently increased the phosphorylation of AMPKα and acetyl-CoA carboxylase (ACC), and inhibited lipogenesis in HepG2 cells. Using compound C, an AMPK inhibitor, or hepatocytes isolated from liver tissue-specific AMPK knockout AMPKα1α2 fl/fl;Alb-cre mice (AMPK LKO), we demonstrated that the lipogenesis inhibition of C24 was dependent on hepatic AMPK activation. In rabbits with high-fat and high-cholesterol diet-induced dyslipidemia, administration of C24 (20, 40, and 60 mg · kg -1 · d -1 , ig, for 4 weeks) dose-dependently decreased the content of TG, total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) in plasma and played a role in protecting against hepatic dysfunction by decreasing lipid accumulation. A lipid-lowering effect was also observed in high-fat and high-cholesterol diet-fed hamsters. In conclusion, our results demonstrate that the small molecular AMPK activator C24 alleviates hyperlipidemia and represents a promising compound for the development of a lipid-lowering drug. |
Full text from SpringerLink