| Project/Area Number |
16590633
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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 | Juntendo University |
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Principal Investigator |
IKEJIMA Kenichi Juntendo University School of Medicine, Department of Gastroenterology, Assistant Professor, 医学部, 講師 (20317382)
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| Co-Investigator(Kenkyū-buntansha) |
TAKEI Yoshiyuki Juntendo University School of Medicine, Department of Gastroenterology, Associate Professor, 医学部, 助教授 (10306954)
ENOMOTO Nobuyuki Juntendo University School of Medicine, Department of Gastroenterology, Assistant Professor, 医学部, 講師 (20348973)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2006: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2005: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | adipocytokines / leptin / adiponectin / nonalcoholic steatohepatitis (NASH) / chronic hepatitis C / interferon / hepatic fibrogenesis / 肝線維化 / アディポネクチン / 低分子量ヘパリン / 抗ウイルス療法 / 肝星細胞 / アポトーシス / 肝類洞壁細胞 |
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| Research Abstract |
In the present study, we investigated the role of adipocytokine in progression and therapeutic responses in chronic liver diseases including non-alcoholic steatohepatitis (NASH) and chronic hepatitis C. To evaluate the role of metabolic factors in progression of steatohepatitis, we utilized KK-Ay mice, which resemble human metabolic syndrome. KK-Ay mice developed more severe steatohepatitis and subsequent hepatic fibrosis as compared to C57B1/6 controls when they were fed a diet lacking methionine and choline (MCD diet). KK-Ay mice not only showed extremely low serum adiponectin levels at basal condition, but also failed to increase serum adiponectin levels following dietary treatment, suggesting that adiponectin plays a key role in prevention of progressive steatohepatitis. On the other hand, we also evaluated whether adipocytokines affect anti-viral effect of interferon in vitro. Leptin blunted anti-viral effect of IFN-a through inhibition of both phosphorylation of STAT-1 and subsequent induction of 2'-5' oligoadenylate synthase (OAS) activity. Moreover, we demonstrated that hepatic steatosis is a predictor of poor sustained viral response (SVR) in interferon and ribavirin combination therapy for chronoc hepatitis C, supporting the hypothesis that host-related metabolic factors modulate therapeutic efficacy of anti-viral therapy in patients with chronic hepatitic C. Collectively, expression pattern of adipocytokines regulates progression and therapeutic responses in metabolic syndrome-related fatty liver diseases and chronic hepatitis C.
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