A rabbit model of pediatric nonalcoholic steatohepatitis: the role of adiponectin.
OBJECTIVE
To create a rabbit model of pediatric nonalcoholic steatohepatitis (NASH) and to evaluate the role of adiponectin in the process.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Fu
Jun-Fen
JF
Department of Endocrinology, The Children's Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China.
Fang
Yan-Lan
YL
Liang
Li
L
Wang
Chun-Lin
CL
Hong
Fang
F
Dong
Guan-Ping
GP
D052242:Adiponectin / Q000097:blood*; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001835:Body Weight / Q000187:drug effects; D004041:Dietary Fats / Q000008:administration & dosage / Q000494:pharmacology; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000097:blood* / Q000473:pathology* / Q000503:physiopathology; D007249:Inflammation / Q000503:physiopathology; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008055:Lipids / Q000097:blood; D008099:Liver / Q000033:anatomy & histology / Q000473:pathology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011817:Rabbits; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D052242:Adiponectin; D004041:Dietary Fats; D015850:Interleukin-6; D008055:Lipids; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase