Yhhu981, a novel compound, stimulates fatty acid oxidation via the activation of AMPK and ameliorates lipid metabolism disorder in ob/ob mice
文献类型：期刊论文
| 作者 | Zeng, Hong-liang; Huang, Su-ling ; Xie, Fu-chun; Zeng, Li-min; Hu, You-hong; Leng, Ying
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| 刊名 | ACTA PHARMACOLOGICA SINICA
 |
| 出版日期 | 2015-03 |
| 卷号 | 36期号:3页码:343-352 |
| 关键词 | yhhu981 fatty acid oxidation fatty acid synthesis AMPK compound C sirtinol EX527 STO609 AICAR metformin metabolism disorder C2C12 myotubes HepG2 cells ob/ob mice |
| ISSN号 | 1671-4083 |
| DOI | 10.1038/aps.2014.147 |
| 文献子类 | Article |
| 英文摘要 | Aim: Defects in fatty acid metabolism contribute to the pathogenesis of insulin resistance and obesity. In this study, we investigated the effects of a novel compound yhhu981 on fatty acid metabolism in vitro and in vivo. Methods: The capacity to stimulate fatty acid oxidation was assessed in C2C12 myotubes. The fatty acid synthesis was studied in HepG2 cells using isotope tracing. The phosphorylation of AMPK and acetyl-CoA carboxylase (ACC) was examined with Western blot analysis. For in vivo experiments, ob/ob mice were orally treated with yhhu981 acutely (300 mg/kg) or chronically (150 or 300 mg.kg(-1).d(-1) for 22 d). On the last day of treatment, serum and tissue samples were collected for analysis. Results: Yhhu981 (12.5-25 mu mol/L) significantly increased fatty acid oxidation and the expression of related genes (Sirt1, Pgc1 alpha and Mcad) in C2C12 myotubes, and inhibited fatty acid synthesis in HepG2 cells. Furthermore, yhhu981 dose-dependently increased the phosphorylation of AMPK and ACC in both C2C12 myotubes and HepG2 cells. Compound C, an AMPK inhibitor, blocked fatty acid oxidation in yhhu981-treated C2C12 myotubes and fatty acid synthesis decrease in yhhu981-treated HepG2 cells. Acute administration of yhhu981 decreased the respiratory exchange ratio in ob/ob mice, whereas chronic treatment with yhhu981 ameliorated the lipid abnormalities and ectopic lipid deposition in skeletal muscle and liver of ob/ob mice. Conclusion: Yhhu981 is a potent compound that stimulates fatty acid oxidation, and exerts pleiotropic effects on lipid metabolism by activating AMPK. |
| WOS关键词 | PROTEIN-KINASE ACTIVATION ; RAT SOLEUS MUSCLE ; SKELETAL-MUSCLE ; INSULIN SENSITIVITY ; MALONYL-COA ; MITOCHONDRIAL BIOGENESIS ; MYOBLAST DIFFERENTIATION ; ENERGY-EXPENDITURE ; DEFICIENT MICE ; GLUCOSE-UPTAKE |
| 资助项目 | National Natural Science Foundation of China[81225022] |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| CSCD记录号 | CSCD:5386861 |
| WOS记录号 | WOS:000351173700006 |
| 出版者 | ACTA PHARMACOLOGICA SINICA |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/276620]  |
| 专题 | 药物化学研究室 中科院受体结构与功能重点实验室 新药研究国家重点实验室 药理学第一研究室 |
| 通讯作者 | Hu, You-hong |
| 作者单位 | Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zeng, Hong-liang,Huang, Su-ling,Xie, Fu-chun,et al. Yhhu981, a novel compound, stimulates fatty acid oxidation via the activation of AMPK and ameliorates lipid metabolism disorder in ob/ob mice[J]. ACTA PHARMACOLOGICA SINICA,2015,36(3):343-352. |
| APA | Zeng, Hong-liang,Huang, Su-ling,Xie, Fu-chun,Zeng, Li-min,Hu, You-hong,&Leng, Ying.(2015).Yhhu981, a novel compound, stimulates fatty acid oxidation via the activation of AMPK and ameliorates lipid metabolism disorder in ob/ob mice.ACTA PHARMACOLOGICA SINICA,36(3),343-352. |
| MLA | Zeng, Hong-liang,et al."Yhhu981, a novel compound, stimulates fatty acid oxidation via the activation of AMPK and ameliorates lipid metabolism disorder in ob/ob mice".ACTA PHARMACOLOGICA SINICA 36.3(2015):343-352. |
入库方式： OAI收割
来源：上海药物研究所
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