2005 Fiscal Year Final Research Report Summary
Investigation in the mechanisms involved in the development of nonalcoholic steatohepatitis and its clinical application
| Project/Area Number |
16590600
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Kochi University |
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Principal Investigator |
SAIBARA Toshiji Kochi University, Kochi Medical School, Department of Gastroenterology and Hepatology, Associated Professor, 医学部, 助教授 (60145125)
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| Co-Investigator(Kenkyū-buntansha) |
TODA Katsumi Kochi University, Kochi Medical School, Department of Biochemistry, Associated Professor, 医学部, 助教授 (40197893)
AKISAWA Naoaki Kochi University, Kochi Medical School, Department of Biochemistry, Assistant Professor, 医学部, 助手 (00322280)
ONO Masafumi Kochi University, Kochi Medical School, Department of Biochemistry, Assistant Professor, 医学部附属病院, 助手 (70304681)
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| Project Period (FY) |
2004 – 2005
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| Keywords | NASH / ANIMAL MODEL / OBESITY / MTP |
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| Research Abstract |
1.Identification of NASH-related genes
We analyzed 240 loci of microsatellites in NASH patients and 4 loci were identified to be involved in the development of NASH. In 3 of the 4 loci, we succeeded in identifying functional single nucleotide polymorphisms of genes in disequilibrium with these microsatellites. All of these functional single nucleotide polymorphisms are frequent in Japanese. These observations could partially explain why NASH is very frequent among Japanese population.
2.Functional analysis of microsomal triglyceride transfer protein
One functional single nucleotide polymorphism was identified to be located in the microsomal triglyceride transfer protein gene that encodes an enzyme involved in conjugating triglycerides with apolipoprotein B. As homozygotes of variant form of this enzyme are impaired in secretion of very low density lipoprotein, they are susceptible to massive hepatic steatosis. Therefore, knockout mouse of microsomal triglyceride transfer protein was developed, but there was no obvious fat deposition in the liver High fat diet also failed to accelerate fat deposition in the liver possibly due to impaired triglyceride uptake in enterocytes since this enzyme is expressed not only in hepatocytes but also in enterocytes. On the contrary, intravenous administration of triglyceride easily induced massive hepatic deposition and provided a useful tool for investigating the mechanism of the development of nonalcoholic steatohepatitis.
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Research Products
(28 results)
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[Book] 肝疾患と免疫2005
Author(s)
西原利治
Total Pages
179
Publisher
医薬ジャーナル社
Description
「研究成果報告書概要(和文)」より
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[Book] 消化器学2005
Author(s)
西原利治
Total Pages
649
Publisher
メジカルビュー社
Description
「研究成果報告書概要(和文)」より
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