Pharmacological inhibition of diacylglycerol acyltransferase 1 reduces body weight gain, hyperlipidemia, and hepatic steatosis in db/db mice
文献类型：期刊论文
| 作者 | Zhang, Xiao-dong1; Yan, Jian-wei1; Yan, Gui-rui1; Sun, Xiao-yun1; Ji, Jun1; Li, Yi-ming2; Hu, You-hong1 ; Wang, He-yao1
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| 刊名 | ACTA PHARMACOLOGICA SINICA
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| 出版日期 | 2010-11 |
| 卷号 | 31期号:11页码:1470-1477 |
| 关键词 | diabetes hepatic steatosis obesity hyperlipidemia small-molecule inhibitor H128 diacylglycerol acyltransferase 1 db/db mice CPT1 gene PPAR alpha gene |
| ISSN号 | 1671-4083 |
| DOI | 10.1038/aps.2010.104 |
| 文献子类 | Article |
| 英文摘要 | Aim: To test whether pharmacological inhibition of Diacylglycerol acyltransferase 1 (DGAT1) by a small-molecule inhibitor H128 can improve metabolism disorders in leptin receptor-deficient db/db mice. Methods: To investigate the effect of H128 on intestinal fat absorption, db/db mice were acutely given a bolus of corn oil by gavage. The mice were further orally administered H128 (3 and 10 mg/kg) for 5 weeks. Blood glucose, lipids, insulin, ALT, and AST as well as hepatic triglycerides were measured. The insulin tolerance test was performed to evaluate insulin sensitivity. The expression of genes involved in fatty acid oxidation was detected by RT-PCR. Results: Oral administration of H128 (10 mg/kg) acutely inhibited intestinal fat absorption following a lipid challenge in db/db mice. Chronic treatment with H128 significantly inhibited body weight gain, decreased food intake, and induced a pronounced reduction of serum triglycerides. In addition, H128 treatment markedly ameliorated hepatic steatosis, characterized by decreased liver weight, lipid droplets, and triglyceride content as well as serum ALT and AST levels. Furthermore, H128 treatment increased the expression of the CPT1 and PPAR alpha genes in liver, suggesting that H128 enhanced fatty acid oxidation in db/db mice. However, neither blood glucose nor insulin tolerance was affected by H128 treatment throughout the 5-week experimental period. Conclusion: DGAT1 may be an effective therapeutic target for the treatment of obesity, hyperlipidemia and hepatic steatosis. |
| WOS关键词 | FATTY-ACID OXIDATION ; ACTIVATED PROTEIN-KINASE ; TRIGLYCERIDE SYNTHESIS ; METABOLIC SYNDROME ; INSULIN-RESISTANCE ; ENERGY-UTILIZATION ; GENE-EXPRESSION ; LIVER-DISEASE ; DGAT ENZYMES ; OBESITY |
| 资助项目 | National Science & Technology Major Project[2009ZX09301-001] ; National High Technology Research and Development Program of China (863 Program)[2007AA02Z301] ; National Natural Science Foundation of China[20972174] ; Shanghai Committee of Science and Technology[10410703900] ; Shanghai Science and Technology Innovation Program[08431900800] ; Shanghai Institutions of Higher Learning[00000000] |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| CSCD记录号 | CSCD:4077143 |
| WOS记录号 | WOS:000284055500009 |
| 出版者 | ACTA PHARMACOLOGICA SINICA |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/278726]  |
| 专题 | 药物化学研究室 药理学第三研究室 |
| 通讯作者 | Hu, You-hong |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China; 2.Shanghai Univ Tradit Chinese Med, Sch Pharm, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhang, Xiao-dong,Yan, Jian-wei,Yan, Gui-rui,et al. Pharmacological inhibition of diacylglycerol acyltransferase 1 reduces body weight gain, hyperlipidemia, and hepatic steatosis in db/db mice[J]. ACTA PHARMACOLOGICA SINICA,2010,31(11):1470-1477. |
| APA | Zhang, Xiao-dong.,Yan, Jian-wei.,Yan, Gui-rui.,Sun, Xiao-yun.,Ji, Jun.,...&Wang, He-yao.(2010).Pharmacological inhibition of diacylglycerol acyltransferase 1 reduces body weight gain, hyperlipidemia, and hepatic steatosis in db/db mice.ACTA PHARMACOLOGICA SINICA,31(11),1470-1477. |
| MLA | Zhang, Xiao-dong,et al."Pharmacological inhibition of diacylglycerol acyltransferase 1 reduces body weight gain, hyperlipidemia, and hepatic steatosis in db/db mice".ACTA PHARMACOLOGICA SINICA 31.11(2010):1470-1477. |
入库方式： OAI收割
来源：上海药物研究所
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