• Original article (Basic research) • Previous Articles     Next Articles

Gender difference and effects in methionine and choline deficient diets-induced non-alcoholic steatohepatitis

ZHANG Qi-juan1, LI Ji-bin2, XIAO Xiao-qiu3, PAN Xian-jun4, PENG Chuan2   

  1. 1.Department of Clinical Nutrition, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China; 2.Department of Nutrition and Food Hygiene, School of Public Health and Management, Chongqing Medical University, Chongqing 400016, China; 3.Laboratory of Lipid & Glucose Metabolism, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China; 4.Department of Endocrine Breast Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
  • Online:2014-01-28 Published:2014-01-29

PDF (PC)

1542

Abstract:

Objective To explore effects of methionine and choline deficient diets (MCD diets) on non-alcoholic steatohepatitis (NASH) development in KM mice, and to study the possible differences between the genders. Methods Three days after delivery, the litter size was adjusted to 10 pups per dam to allow comparable calorie intakes during lactation. After weaning, the pups were fed with standard diets until 10 weeks. Then the offspring were randomly divided into four groups: female control group (F-CTR), female MCD diets group (F-MCD), male control group (M-CTR), and male MCD diets group (M-MCD). Mice in control or MCD groups were fed with standard or MCD diets respectively for 4 weeks. The body weights were recorded once a week. The samples of serum and liver tissue were obtained after sacrificing. Liver morphologic analysis was performed by HE staining; The ultra-structure of hepatocyte was observed using transmission electron microscope. Serum alanine aminotransferase (ALT) and aspartate transaminase (AST) were determined by automatic biochemical analyzing system. The mRNA levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were determined by qualitative Real-time PCR. Results The body weights of male mice were higher than those of female mice before 11 weeks of age (P<0.05). After MCD diets were induced, the body weights declined significantly compared with those fed with standard diets. In MCD groups, HE staining showed typical characteristics of NASH, including steatosis, hepatocyte ballooning, and inflammatory cells infiltration. Moreover, in MMCD group, the changes of NASH were more severe. Serum AST and AST levels were higher in M-MCD group than those in F-MCD group. The mRNA levels of TNF-α, but not IL-6, were also higher in M-MCD group than those in F-MCD group (P<0.05). Conclusion Deficiency in methionine and choline induced typical pathological changes of NASH in KM mice. This could serve as an ideal animal model for non-alcoholic fatty liver disease (NAFLD) research work. Male mice were more susceptible to MCD diets-induced NASH compared with female mice, with more severe inflammation. Up-regulation of TNF-α expression may participate in the inflammatory injury in mice.

Key words: non-alcoholic steatohepatitis, hepatocyte ballooning, inflammation