In vivo delivery of cell-permeable antisense hypoxia-inducible factor 1 alpha oligonucleotide to adipose tissue reduces adiposity in obese mice
文献类型：期刊论文
| 作者 | Park, Yoon Shin2; David, Allan E.2; Huang, Yongzhuo3 ; Park, Jun-Beom4; He, Huining1,5; Byun, Youngro4; Yang, Victor C.1,2,4,5
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| 刊名 | JOURNAL OF CONTROLLED RELEASE
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| 出版日期 | 2012-07-10 |
| 卷号 | 161期号:1页码:1-9 |
| 关键词 | Antisense oligonucleotide Obesity Hypoxia inducible factor 1 alpha Low molecular weight protamine Angiogenesis Adipogenesis |
| ISSN号 | 0168-3659 |
| DOI | 10.1016/j.jconrel.2012.04.026 |
| 文献子类 | Article |
| 英文摘要 | Ongoing research has gradually recognized and understood the importance of adipose tissue (AT) angiogenesis as a key modulating factor of adipogenesis in the development of obesity. Previously, we carried out the first in vitro demonstration of the down-regulation of hypoxic angiogenesis during adipogenesis using cell-permeable chemical conjugates composed of antisense hypoxia-inducible factor 1 alpha (HIF1 alpha) oligonucleotide (ASO) and low-molecular weight protamine (LMWP). To further confirm the in vivo feasibility, we administered ASO-LMWP conjugates (AL) to diet-induced obese (DIO) mice by intraperitoneal injection (IP). Results showed that the AL conjugates significantly reduced the body weight, total fat tissue weight, and plasma lipid concentrations in the mice. Moreover, the AL conjugates not only decreased liver weight and hepatic triglyceride concentration but also significantly attenuated subcutaneous adipocyte cell size, which was conversely increased in the AL-untreated high-fat diet (HFD) group. Interestingly, more blood vessels were observed in the HFD group than in the lean group, indicating that blood vessel development could induce growth of the fat mass. This pattern was reversed in the AL-treated groups, which displayed a decrease in blood vessel density compared to the AL-untreated HFD group. This study presents the first in vivo evidence, in an obese mouse model, of the feasibility of achieving a biological treatment modality for obesity by blocking the angiogenic transcriptional factor HIF1 alpha, thereby limiting angiogenesis, via the use of an adipose tissue-permeable ASO-LMWP. (C) 2012 Elsevier B.V. All rights reserved. |
| WOS关键词 | GENE-TRANSFER ; INTRACELLULAR DELIVERY ; ANGIOGENESIS ; THERAPEUTICS ; EXPRESSION ; THERAPY ; PEPTIDE ; CANCER ; COMBINATION ; SIBUTRAMINE |
| 资助项目 | NIH[CA114612] ; World Class University (WCU) project of the MEST[R31-2008-000-10103-01] ; NRF of South Korea[00000000] |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000305790100001 |
| 出版者 | ELSEVIER SCIENCE BV |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/278016]  |
| 专题 | 药物制剂研究中心 |
| 通讯作者 | Yang, Victor C. |
| 作者单位 | 1.Tianjin Key Lab Technol Enabling Dev Clin Therape, Tianjin 300070, Peoples R China 2.Univ Michigan, Coll Pharm, Dept Pharmaceut Sci, Ann Arbor, MI 48109 USA; 3.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China; 4.Seoul Natl Univ, Grad Sch Convergence Sci & Technol, Dept Mol Med & Biopharmaceut Sci, Seoul, South Korea; 5.Tianjin Med Univ, Sch Pharm, Tianjin 300070, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Park, Yoon Shin,David, Allan E.,Huang, Yongzhuo,et al. In vivo delivery of cell-permeable antisense hypoxia-inducible factor 1 alpha oligonucleotide to adipose tissue reduces adiposity in obese mice[J]. JOURNAL OF CONTROLLED RELEASE,2012,161(1):1-9. |
| APA | Park, Yoon Shin.,David, Allan E..,Huang, Yongzhuo.,Park, Jun-Beom.,He, Huining.,...&Yang, Victor C..(2012).In vivo delivery of cell-permeable antisense hypoxia-inducible factor 1 alpha oligonucleotide to adipose tissue reduces adiposity in obese mice.JOURNAL OF CONTROLLED RELEASE,161(1),1-9. |
| MLA | Park, Yoon Shin,et al."In vivo delivery of cell-permeable antisense hypoxia-inducible factor 1 alpha oligonucleotide to adipose tissue reduces adiposity in obese mice".JOURNAL OF CONTROLLED RELEASE 161.1(2012):1-9. |
入库方式： OAI收割
来源：上海药物研究所
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