Effect of calories restriction on ER stress in the liver of high fat diet rats / 中国病理生理杂志

ABSTRACT

AIM: To study the effect of calories restriction on endoplasmic reticulum(ER) chaperone protein 78-kD glucose regulated protein(GRP78) mRNA expression in the liver of high fat diet rats,in order to explore the mechanism of how calories restriction improves insulin resistance.METHODS: Wistar rats(n=24) were randomly divided into 3 groups normal chow(NC) group,was fed free normal chow(18.94% of calories as fat) for 12 weeks;high fat group(HF) was fed high fat diet(50.55% of calories as fat) for 12 weeks;calories restriction group(CR) was fed high fat diet for 8 weeks at first,then given 50% of diet consumed by the same age NC group.Changes of body weight,height,and food intake were recorded.At the end of experiment,HOMAIR,the rate of visceral fat(including perirenal fat and epididymal fat) vs weight,plasma protein,blood lipid(including total cholesterol and triglyceride),hepatic GRP78 mRNA and hepatic histological changes(including light microscopic studies and electron microscopic studies) were detected.RESULTS:(1) Animals in HF group had an obviously elevation of fasting insulin(27.51?3.51) mU/L vs(15.46?2.25) mU/L,triglyceride(1.35?0.25) mmol/L vs(0.67?0.10) mmol/L,total cholesterol(2.59?0.34) mmol/L vs(1.41?0.28) mmol/L and insulin resistance index HOMAIR(5.85?0.23 vs 2.85?0.60) compared with NC group,and also had obviously lipid accumulations in the liver.(2) After calories restriction,all the abnormal elevated biochemical indicators were decreased to normal levels,the hepatic lipid accumulations were also improved.(3) The changes of liver ultrastructure in HF group showed rough endoplasmic reticulum enlargement,fragmentation,taking off grain,and with glycogen solution.The changes in CR group were nearly the same as those in NC group.(4) High fat diet induced the expression of GRP78 mRNA, calories restriction might reverse it.CONCLUSION: Reasonable food calories restriction is a good method to improve insulin resistance,partly due to improvement of endoplasmic reticulum stress in liver.