ABSTRACT
Objective To observe the effect of tumor necrosis factor-α( TNF-α) on islet cell apoptosis and TXNIP expression.Methods INS-1 cells were cultured in vitro, treating with TNF-α(0, 1, 5, 10 and 20 mg/L).We tested the effect of TNF-αon cell viability by CCK-8.INS-1 cells were treated with TNF-α( 5 mg/L, 24 h) for the proper concentration and incubation time; mRNA expression of TXNIP and ChREBP were measured by real-time PCR;in addition, protein levels of TXNIP , ChREBP and FOXO1 were analyzed by Western blot .Results TNF-αdecreased the survival rate of INS-1 cells in a dose-dependent manner ( P<0.05 ) , and induced apoptosis;protein and mRNA expression of TXNIP and ChREBP were significantly higher than that in control group ( P<0.05 );while the expression of protein level of FOXO 1 was down-regulated .Conclusions TNF-αinduces apoptosis in INS-1 cells and aggravates the cells damage .
ABSTRACT
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is increasingly recognized as a major cause of liver-related morbidity and mortality. The underlying mechanisms of disease progression remain poorly understood, and primary therapy of NAFLD is not yet established. We investigated the effects of dietary oleate on the development and progression of NAFLD in a methionine- and choline-deficient (MCD) diet-fed animal model. METHODS: A total of 30 C57BL/6J mice were randomly divided into three groups (n=10 in each group) and fed various experimental diets for four weeks: chow, MCD diet, or OMCD (MCD diet with oleate, 0.5 mg/g/day). Liver samples were examined for steatohepatitis and fibrosis parameters and associated genes. RESULTS: Additional dietary oleate dramatically reduced MCD diet-induced hepatic steatosis. Hepatic carbohydrate responsive element-binding protein was overexpressed in MCD diet-fed mice, and dietary oleate prevented this overexpression (P<0.001). Dietary oleate partially prevented MCD diet-induced serum level increases in aspartate aminotransferase and alanine aminotransferase (P<0.001, respectively). The mRNA expressions of hepatic monocyte chemoattractant protein 1, tumor necrosis factor-alpha and matrix metalloproteinase-9 were increased in MCD diet-fed mice, and this overexpression of inflammatory molecules was prevented by dietary oleate (P<0.001). Hepatic pericellular fibrosis was observed in MCD diet-fed mice, and dietary oleate prevented this fibrosis. Altogether, dietary oleate prevented MCD diet-induced hepatic steatosis, inflammation and fibrosis. CONCLUSION: Dietary oleate has beneficial effects in every step of NAFLD development and progression and could be a nutritional option for NAFLD prevention and treatment.