A rabbit model of pediatric nonalcoholic steatohepatitis: the role of adiponectin.

Abstract

To create a rabbit model of pediatric nonalcoholic steatohepatitis (NASH) and to evaluate the role of adiponectin in the process. Thirty-two specific pathogen-free male New Zealand rabbits were divided randomly into three groups: (1) the normal control group (n = 10) was fed with standard diet for 12 wk; (2) the model group A (n = 11); and (3) model group B (n = 11) were fed with a high-fat diet (standard diet + 10% lard + 2% cholesterol) for 8 and 12 wk, respectively. Hepatic histological changes were observed and biochemical parameters as well as serum levels of adiponectin, interleukin (IL)-6, IL-10 and tumor necrosis factor (TNF)-alpha were measured. Typical histological hepatic lesions of NASH were observed in both model groups described as liver steatosis, liver inflammatory infiltration, cytologic ballooning, perisinusoidal fibrosis and overall fibrosis. Compared with the normal control group, there were significant increases in model groups A and B in weight gain (1097.2 +/- 72.3, 1360.5 +/- 107.6 vs 928.0 +/- 58.1, P < 0.05, P < 0.01), liver weight (93.81 +/- 6.64, 104.6 +/- 4.42 vs 54.4 +/- 1.71, P < 0.01), Lg (ALT) (1.9 +/- 0.29, 1.84 +/- 0.28 vs 1.60 +/- 0.17, P < 0.01), and Lg (TG) (1.03 +/- 0.24, 1.16 +/- 0.33 vs 0.00 +/- 0.16, P < 0.01). Weight gain was much more in model group B than in model group A (1360.5 +/- 107.6 vs 1097.2 +/- 72.3, P < 0.05). But, there was no significant difference between the two groups concerning the other indexes. Pro-inflammatory cytokines (IL-6 and TNF-alpha) increased in model group B compared with that of control and model group A (IL-6: 1.86 +/- 0.21 vs 1.41 +/- 0.33, 1.38 +/- 0.42, P < 0.01; TNF-alpha: 1.18 +/- 0.07 vs 0.66 +/- 0.08, 0.86 +/- 0.43, P < 0.01, P < 0.05), whereas serum adiponectin and IL-10 decreased in model groups compared with that in the control (adiponectin: A: 21.87 +/- 4.84 and B: 21.48 +/- 4.60 vs 27.36 +/- 7.29, P < 0.05. IL-10: A: 1.72 +/- 0.38 and B: 1.83 +/- 0.39 vs 2.26 +/- 0.24, P < 0.01). Lg (TC) and the degree of liver fatty infiltration was an independent determinant of serum adiponectin level analyzed by stepwise multiple regressions, resulting in 29.4% of variances. This rabbit model produces the key features of pediatric NASH and may provide a realistic model for future studies. Adiponectin level partially reflects the severity of liver steatosis, but not the degree of liver inflammation.