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Hepatic Monoacylglycerol O-acyltransferase 1 as a Promising Therapeutic Target for Steatosis, Obesity, and Type 2 Diabetes
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| Title: | Hepatic Monoacylglycerol O-acyltransferase 1 as a Promising Therapeutic Target for Steatosis, Obesity, and Type 2 Diabetes |
| Authors: | Hayashi, Yasuhiro Browse this author →KAKEN DB | | Suemitsu, Erina Browse this author | | Kajimoto, Kazuaki Browse this author →KAKEN DB | | Sato, Yusuke Browse this author | | Akhter, Afsana Browse this author | | Sakurai, Yu Browse this author | | Hatakeyama, Hiroto Browse this author →KAKEN DB | | Hyodo, Mamoru Browse this author →KAKEN DB | | Kaji, Noritada Browse this author →KAKEN DB | | Baba, Yoshinobu Browse this author →KAKEN DB | | Harashima, Hideyoshi Browse this author →KAKEN DB |
| Keywords: | in vivo siRNA delivery | | liver | | microarray | | monoacylglycerol O-acyltransferase 1 (Mogat1) | | type 2 diabetes |
| Issue Date: | 18-Mar-2014 |
| Publisher: | Nature Publishing Group |
| Journal Title: | Molecular Therapy - Nucleic Acids |
| Volume: | 3 |
| Start Page: | e154 |
| Publisher DOI: | 10.1038/mtna.2014.4 |
| Abstract: | Over the past decade, considerable advances have been made in the discovery of gene targets in metabolic diseases. However, in vivo studies based on molecular biological technologies such as the generation of knockout mice and the construction of short hairpin RNA vectors require considerable effort and time, which is a major limitation for in vivo functional analysis. Here, we introduce a liver-specific nonviral small interfering RNA (siRNA) delivery system into rapid and efficient characterization of hepatic gene targets in metabolic disease mice. The comparative transcriptome analysis in liver between KKAy diabetic and normal control mice demonstrated that the expression of monoacylglycerol O-acyltransferase 1 (Mogat1), an enzyme involved in triglyceride synthesis and storage, was highly elevated during the disease progression. The upregulation of Mogat1 expression in liver was also found in other genetic (db/db) and diet-induced obese mice. The silencing of hepatic Mogat1 via a liver-specific siRNA delivery system resulted in a dramatic improvement in blood glucose levels and hepatic steatosis as well as overweight with no apparent overall toxicities, indicating that hepatic Mogat1 is a promising therapeutic target for metabolic diseases. The integrated approach with transcriptomics and nonviral siRNA delivery system provides a blueprint for rapid drug discovery and development. |
| Rights: | http://creativecommons.org/licenses/by-nc-nd/3.0/ |
| Type: | article |
| URI: | http://hdl.handle.net/2115/57440 |
| Appears in Collections: | 薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 梶本 和昭
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