Diet-induced Nonalcoholic Steatohepatitis In Mice Research Articles

Omega-3 polyunsaturated fatty acid and ursodeoxycholic acid have an additive effect in attenuating diet-induced nonalcoholic steatohepatitis in mice.

Nonalcoholic steatohepatitis (NASH) can progress into liver cirrhosis; however, no definite treatment is available. Omega-3 polyunsaturated fatty acid (omega-3) has been reported to alleviate experimental NASH, although its beneficial effect was not evident when tested clinically. Thus, this study aimed to investigate the additive effect of omega-3 and ursodeoxycholic acid (UDCA) on diet-induced NASH in mice. C57BL/6 mice were given a high-fat diet (HFD) for 24 weeks, at which point the mice were divided into three groups and fed HFD alone, HFD with omega-3 or HFD with omega-3 in combination with UDCA for another 24 weeks. Feeding mice an HFD and administering omega-3 improved histologically assessed liver fibrosis, and UDCA in combination with omega-3 further attenuated this disease. The assessment of collagen α1(I) expression agreed with the histological evaluation. Omega-3 in combination with UDCA resulted in a significant attenuation of inflammation whereas administering omega-3 alone failed to improve histologically assessed liver inflammation. Quantitative analysis of tumor necrosis factor α showed an additive effect of omega-3 and UDCA on liver inflammation. HFD-induced hepatic triglyceride accumulation was attenuated by omega-3 and adding UDCA accentuated this effect. In accordance with this result, the expression of sterol regulatory binding protein-1c decreased after omega-3 administration and adding UDCA further diminished SREBP-1c expression. The expression of inducible nitric oxide synthase (iNOS), which may reflect oxidative stress-induced tissue damage, was suppressed by omega-3 administration and adding UDCA further attenuated iNOS expression. These results demonstrated an additive effect of omega-3 and UDCA for alleviating fibrosis, inflammation and steatosis in diet-induced NASH.

Inhibition of aldose reductase ameliorates diet-induced nonalcoholic steatohepatitis in mice via modulating the phosphorylation of hepatic peroxisome proliferator-activated receptor α.

Aldose reductase (AR) is involved in the pathogenesis of nonalcoholic steatohepatitis. This study aimed to determine the mechanism by which AR affects the development of murine diet-induced nonalcoholic steatohepatitis. Steatohepatitis was induced in C57BL/6 mice by administration of a methionine-choline-deficient (MCD) diet, a commonly used nutrition-induced model of steatohepatitis. Hematoxylin and eosin staining was used for histological analyses. Western blot analyses were used to determine protein expression levels and quantitative polymerase chain reaction was used to analyze mRNA expression levels. The results showed that the AR protein expression level was significantly higher in C57BL/6 mice fed the MCD diet than in mice fed the control diet. Diet-induced hepatic steatosis and necroinflammation were attenuated in the MCD diet-fed mice treated with the AR inhibitor, zopolrestat. The ameliorating effect of AR inhibition on steatohepatitis was associated with decreased levels of serum alanine aminotransferase and hepatic lipoperoxides, reduced expression of phosphorylated peroxisome proliferator-activated receptor (PPAR)α and increased mRNA expression of acyl coenzyme A oxidase. These data indicated that induction of hepatic AR expression in mice with steatohepatitis resulted in the phosphorylation of PPARα and suppression of PPARα activity. Inhibition of AR decreased lipid accumulation and inflammation in the liver, at least in part through the modulation of PPARα phosphorylation and PPARα transcriptional activity.

395 Protective Effect of the Postaglandin I2-IP Signal in Mcd Diet-Induced Nonalcoholic Steatohepatitis in Mice

395 Protective Effect of the Postaglandin I2-IP Signal in Mcd Diet-Induced Nonalcoholic Steatohepatitis in Mice

Dmbt1 does not affect a Western style diet-induced liver damage in mice

In the last three decades the prevalence of non-alcoholic fatty liver disease has markedly increased. Results from epidemiologic studies indicate that not only a general overnutrition but rather a diet rich in sugar, fat and cholesterol (= Western style diet) maybe a risk factor for the development of non-alcoholic fatty liver disease. Concerning liver diseases, it is known that Deleted in malignant brain tumors 1 is amongst others related to liver injury and repair. In addition Deleted in malignant brain tumors 1 seems to play a role in regard to the maintenance of the intestinal homeostasis and the regulation of food intake. Starting from this background the aim of the present study was to investigate if Dmbt1 plays a role in Western style diet-induced non-alcoholic steatohepatitis in mice. Dmbt1+/+ and Dmbt1−/− mice were fed a Western style diet or control diet ad libitum for 12 weeks. Both Western style diet fed groups gained significant more weight than the controls and developed a mild non-alcoholic steatohepatitis. The presence/absence of functional Deleted in malignant brain tumors 1 had no effect on parameters like food intake, weight gain, fasting glucose, and liver damage. These results suggest that Deleted in malignant brain tumors 1 plays a minor part on the development of a diet-induced liver damage in mice.