AMPK activator C24 inhibits hepatic lipogenesis and ameliorates dyslipidemia in HFHC diet-induced animal models
文献类型：期刊论文
| 作者 | Sun, Shui-mei1,2; Xie, Zhi-fu2; Zhang, Yang-ming1,2,4 ; Zhang, Xin-wen2; Zhou, Chen-dong2; Yin, Jian-peng4; Yu, Yan-yan2; Cui, Shi-chao2; Jiang, Hao-wen2; Li, Teng-teng1,2,3
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| 刊名 | ACTA PHARMACOLOGICA SINICA
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| 出版日期 | 2020-07-28 |
| 页码 | 8 |
| 关键词 | adenosine 5 '-monophosphate-activated protein kinase AMPK activator C24 liver triglycerides cholesterol VLDL hypolipidemic drug metabolic syndrome |
| ISSN号 | 1671-4083 |
| DOI | 10.1038/s41401-020-0472-9 |
| 通讯作者 | Nan, Fa-jun(fjnan@simm.ac.cn) ; Li, Jing-ya(jyli@simm.ac.cn) |
| 英文摘要 | 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 mu M) dose-dependently increased the phosphorylation of AMPK alpha 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 AMPK alpha 1 alpha 2(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 center dot kg(-1)center dot 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. |
| WOS关键词 | PROTEIN-KINASE CASCADE ; FATTY-ACID ; CHOLESTEROL-SYNTHESIS ; ATHEROSCLEROSIS ; HOMEOSTASIS ; INSULIN ; METABOLISM ; LIVER ; STEATOSIS ; TARGETS |
| 资助项目 | National Natural Science Foundation of China[81673493] ; National Natural Science Foundation of China[81273566] ; National Natural Science Foundation of China[81803596] ; National Key New Drug Creation and Manufacturing Program, Ministry of Science and Technology[2018ZX09711002] |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000553293400003 |
| 出版者 | NATURE PUBLISHING GROUP |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/292215]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Nan, Fa-jun; Li, Jing-ya |
| 作者单位 | 1.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China 3.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China 4.Yantai Inst Mat Med, Yantai Key Lab Nanomed & Adv Preparat, Yantai 264000, Peoples R China |
| 推荐引用方式 GB/T 7714 | Sun, Shui-mei,Xie, Zhi-fu,Zhang, Yang-ming,et al. AMPK activator C24 inhibits hepatic lipogenesis and ameliorates dyslipidemia in HFHC diet-induced animal models[J]. ACTA PHARMACOLOGICA SINICA,2020:8. |
| APA | Sun, Shui-mei.,Xie, Zhi-fu.,Zhang, Yang-ming.,Zhang, Xin-wen.,Zhou, Chen-dong.,...&Li, Jing-ya.(2020).AMPK activator C24 inhibits hepatic lipogenesis and ameliorates dyslipidemia in HFHC diet-induced animal models.ACTA PHARMACOLOGICA SINICA,8. |
| MLA | Sun, Shui-mei,et al."AMPK activator C24 inhibits hepatic lipogenesis and ameliorates dyslipidemia in HFHC diet-induced animal models".ACTA PHARMACOLOGICA SINICA (2020):8. |
入库方式： OAI收割
来源：上海药物研究所
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