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F atty liver S hionogi‐ ob/ob mouse: A new candidate for a non‐alcoholic steatohepatitis model
Author(s) -
Sugihara Takaaki,
Koda Masahiko,
Kishina Manabu,
Kato Jun,
Tokunaga Shiho,
Matono Tomomitsu,
Ueki Masaru,
Murawaki Yoshikazu
Publication year - 2013
Publication title -
hepatology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.123
H-Index - 75
eISSN - 1872-034X
pISSN - 1386-6346
DOI - 10.1111/j.1872-034x.2012.01101.x
Subject(s) - steatohepatitis , fatty liver , medicine , endocrinology , disease
Aim The fatty liver S hionogi ( FLS ) mouse develops hereditary fatty liver without obesity. The FLS ‐ ob/ob mouse made by transferring the leptin ob gene demonstrates several metabolic disorders and marked fat deposition in the liver. The aim was to evaluate which mouse model, the FLS or FLS ‐ ob/ob , is more useful for non‐alcoholic steatohepatitis research. Methods FLS ( n = 40) and FLS ‐ ob/ob ( n = 40) mice were fed a standard diet for 12, 24, 36 and 48 weeks, and then killed. The degree of fat deposition, oxidative stress, fibrosis and apoptosis were analyzed in the liver. Hepatic m RNA expression of fibrogenic and pro‐inflammatory cytokines was measured. Results FLS mice developed hepatic steatosis and slight fibrosis without obesity between 12 and 48 weeks of age. Conversely, FLS ‐ ob/ob mice developed severe steatosis at 12 weeks of age, and steatohepatitis with increased oxidative stress and advanced fibrosis between 24 and 36 weeks of age. At 48 weeks of age, some FLS ‐ ob/ob but not FLS mice, progressed to cirrhosis. Transforming growth factor‐β1, connective tissue growth factor and tumor necrosis factor‐α m RNA expression levels were greater in FLS ‐ ob/ob than FLS mice between 24 and 48 weeks of age. The number of apoptotic cells in the liver was greater at 12 weeks of age in FLS mice and at 48 weeks of age in FLS ‐ ob/ob mice. Conclusion FLS ‐ ob/ob mice developed more severe steatohepatitis with fibrosis than FLS mice, and had increased oxidative stress and apoptosis. These findings indicate that the FLS ‐ ob/ob mouse is a more useful model for steatohepatitis research.