The effect of rosiglitazone on casein-induced hepatic ER stress in animal model
카제인으로 유도된 간의 소포체 스트레스에 로시클리타존이 미치는 영향
Dept. of Medical Science/석사
BACKGROUNDCow`s milk proteins have been reported as one of the substances that cause systemic inflammation triggered by immune response system. And recently, it is well known that ER stress is involved in the development of insulin resistance and type 2 diabetes mellitus, and Thiazolidinediones (TZDs) is an anti-diabetic agent acting as a potent insulin sensitizer. So, there have been many efforts to investigate the effect of TZDs on ER stress. However, the effect of TZDs on ER stress is still controversial. So, in this study, we want to investigate whether the major cow’s milk protein, casein, induces ER stress in liver of rodent model, and rosiglitazone can attenuate these changes.MATERIALS AND METHODSNine-week-old male Sprague-Dawley (SD) rats (n=30) were separated into three groups: (1) vehicle treated (n=10); (2) daily subcutaneous injections of 1 mL 10% casein treated (n=10); (3) daily subcutaneous injection of 1mL 10% casein and rosiglitazone 4 mg/[kg d] treated. After 6 weeks, body weight, food intake, body temperature, fasting plasma glucose, fasting insulin, lipid profile, and serum AST/ALT levels were measured in the morning after an overnight fast. Real time RT-PCR and immunohistochemical staining for various ER stress markers were performed and TUNEL analysis was done. RESULTSAfter 6wks, casein injection induced weight reduction, systemic inflammation, and hepatic dysfunction in SD rats. Casein injection increased ER stress markers in liver in gene expression and protein expression, and caused hepatocyte apoptosis. Rosiglitazone treatment attenuated casein-induced systemic inflammation, ER stress, deteriorated liver function, and increased apoptosis. CONCLUSIONIn this study, we found that casein injection induced ER stress in the liver, worsened liver function, and caused cellular apoptosis. And simultaneous rosiglitazone treatment prevented this casein-induced ER stress and the concomitant changes. Our results may provide further insight into the effects of casein on chronic inflammatory diseases, and the additional mechanism of anti-inflammatory action of rosiglitazone.