2006 Fiscal Year Final Research Report Summary
Role of adipocytokine in progression and therapeutic resistance in chronic liver diseases and hepatocellular carcinoma
| 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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| Keywords | adipocytokines / leptin / adiponectin / nonalcoholic steatohepatitis (NASH) / chronic hepatitis C / interferon / hepatic fibrogenesis / 肝線維化 |
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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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[Journal Article] Expression of leptin receptors in hepatic sinusoidal cells.2004
Author(s)
Ikejima K, Lang T, Zhang YJ, Yamashina S, Honda H, Yoshikawa M, Hirose M, Enomoto N, Kitamura T, Takei Y, Sato N.
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Journal Title
Comparative Hepatology3 (Suppl I) S12
Description
「研究成果報告書概要(欧文)」より
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