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Role of adipocytokines in hepatic fibrogenesis
Author(s) -
Ikejima Kenichi,
Okumura Kyoko,
Kon Kazuyoshi,
Takei Yoshiyuki,
Sato Nobuhiro
Publication year - 2007
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/j.1440-1746.2007.04961.x
Subject(s) - steatohepatitis , hepatic stellate cell , medicine , endocrinology , steatosis , downregulation and upregulation , adiponectin , hepatic fibrosis , adipokine , leptin , fibrosis , insulin resistance , fatty liver , inflammation , insulin , biology , obesity , biochemistry , disease , gene
Obesity and insulin resistance are the key factors for progression of hepatic fibrosis in various chronic liver diseases including non‐alcoholic steatohepatitis (NASH). Recently it has been shown that leptin plays a pivotal role in development of hepatic fibrosis. Leptin promotes hepatic fibrogenesis through upregulation of transforming growth factor‐β in Kupffer cells and sinusoidal endothelial cells. Further, leptin facilitates proliferation and prevents apoptosis of hepatic stellate cells. There is a paradox, however, in that ob/ob mice and Zucker rats, which are the obese and diabetic strains, had minimal profibrogenic responses in the liver, most likely because they lack leptin and its receptors. To establish a more clinically relevant model to study the mechanism of fibrogenesis under steatohepatitis, fatty changes and profibrogenic responses in the liver caused by methionine–choline deficiency (MCD) were investigated in the KK‐A y mouse, which is an obese and diabetic strain. KK‐A y mice developed more severe hepatic steatosis, inflammation and fibrosis induced by an MCD diet as compared to C57Bl/6 controls. Importantly, KK‐A y mice lack physiological upregulation of adiponectin levels, suggesting that adiponectin plays a pivotal role not only in regulation of insulin sensitivity but also in modulation of inflammatory and profibrogenic responses in dietary steatohepatitis. Collectively, these findings support the hypothesis that the balance of adipocytokine expression is a key regulator for the progression of hepatic fibrosis in the setting of steatohepatitis.