2007 Fiscal Year Final Research Report Summary
Involvement of Angpt14 in the pathological mechanisms of steatosis and steatohepatitis
| Project/Area Number |
18590746
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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 | Keio University |
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Principal Investigator |
TOMITA Kengo Keio University, School of Medicine, Assistant Professor (50317129)
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| Project Period (FY) |
2006 – 2007
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| Keywords | steatohepatitis / Angiopoietin like protein |
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| Research Abstract |
Nonalcoholic fatty liver disease can be characterized as a hepatic manifestation of a metabolic syndrome. Nonalcoholic steatohepatitis (NASH) is a severe form of this disease. Angptl4, a member of the angiopoietin-like protein family, is primarily secreted by the liver and adipose tissue. It directly inhibits lipoprotein lipase (LPL) activity and elevates serum triglyceride (TG) level. It has also been reported to improve insulin resistance. Since it is secreted by the liver and involved in the regulation of lipid metabolism and insulin resistance, Angptl4 is a potential therapeutic target for metabolic syndrome. It has also been suggested to be closely associated with the pathology of NASH, for which metabolic syndrome is a background factor. Therefore, Angptl4 is also a potential target for new therapeutic strategies for NASH. In the present study, we established a mouse model of NASH using a methionine-choline deficient (MCD) diet, and examined Angptl4 expression in the liver of these mice. The level of hepatic expression of Angptl4 mRNA was significantly lower in groups of mice that were placed on the MCD diet for three or eight weeks than in the control group, suggesting the possibility that decreased Angptl4 expression in the liver is part of the pathological mechanism of NASH. We also separated parenchymal and nonparenchymal cells and examined the expression of Angptl4 mRNA in each fraction. Angptl4 mRNA was largely expressed in hepatocytes. Further study is necessary to determine the importance of this result for the pathological mechanism of NASH.
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