Effect Of High-fructose Diet On ChREBP, SREBP-1c Expression In Rat Liver

Objective: To explore the effect of high fructose feeding on rat liverlipid synthesis by observing the mRNA and protein expression ofcarbohydrate responsive element binding protein (ChREBP), sterol regulatoryelement binding protein-1c (SREBP-1c) and their target genes in liver inWistar rat fed on high-fructose diet.Methods: Totally48rats were randomly divided into2groups: normalcontrol group (NC, n=24) and high-fructose diet group (HF, n=24). The rats inNC group were fed on a normal diet, with the energy contents as follows:65.5%of carbohydrate,24.2%of protein and10.3%of fat; while the rats inHF group were fed on a high-fructose diet, with the energy contents asfollows:77%of carbohydrate (34.5%of fructose),16%of protein and7%offat. At the end of the8th week and16th week, the rats were respectivelykilled, then blood samples and the liver were simultaneously collected. Beforethe rats were executed, each group of rats were fasted for12hours and oralglucose tolerance test (OGTT) and hyperinsulinemic-euglycemic clamp testwere performed. Area under curve of blood glucose (AUCglu) and glucoseinfusion rate (GIR) were calculated. After body weight and liver weight weremeasured, the ratio of body weight to liver weight (hepatosomatic index) wascalculated. Blood samples were collected from carotid arter. Serumtriglyceride (TG), total cholesterol (TC), free fatty acids (FFAs), alanineaminotransferase (ALT), aspartate aminotransferase (AST), fasting bloodglucose (FBG), and fasting serum insulin (FINS) were detected. Liverpathology examination was carried out to observe the lipid deposits, and thecontent of the liver triglyceride was measured. The mRNA and proteinexpression of carbohydrate responsive element binding protein (ChREBP),sterol regulatory element binding protein-1c (SREBP-1c), fatty acid synthetase (FAS) and acetyl-CoA carboxylase (ACC) in liver were analyzedby RT-PCR and Western Blotting respectively.Results:(1) Rat body weight, hepatosomatic index and serumbiochemical index:①At the end of8th week and16th week, there was no significantdifference in body weight in each group(P＞0.05). At8th week and16thweek, hepatosomatic index was notably higher in HF group compared withNC group (P<0.01).②At the end of8th week and16th week, serum ALT,AST,TG and TC inHF group were obviously higher than in NC group (P<0.01).(2) Oral glucose tolerance test (OGTT): At8th week and16th week, areaunder the curve of glucose (AUCglu) was significantly higher in HF group incomparison with NC group (P<0.01).(3) At8th week and16th week, FBG and FINS were significantly higherin HF group compared with NC group (P<0.01); while glucose infusion rate(GIR) was dramatically lower in HF group in comparison with NC group(P<0.01).(4) At the end of8th week and16th week, free fatty acids (FFA) wasmarkedly higher in HF group compared with NC group (P<0.01).(5) Liver triglyceride (TG) levels: at the end of8th week and16th week,the content of the liver triglyceride was significantly higher in HF groupcompared with NC group (P<0.01).(6) At the end of8th week, there were obvious hepatic steatosis and lipiddeposition in liver tissues of HF group, and at the end of16th week, hepaticsteatosis and lipid deposition were even more remarkable.(7) At the end of8th week and16th week, ChREBP, SREBP-1c, FAS,ACC mRNA and protein expression were up regulated in HF group incomparison with the NC group (P<0.01), furthermore, the mRNA and proteinexpression at16th week remarkably higher than that at the end of8th week(P<0.01).Conclusions:(1)High fructose feeding induces rat hypertriglyceridemia and insulin resisitance.(2) High fructose feeding leads to hepatic steatosis and liver lipiddeposition.(3) High fructose feeding up-regluates the mRNA and protein expressionof ChREBP,SREBP-1c and their target genes FAS,ACC in the liver, whichresults in a increased liver triglyceride synthesis and leads to the developmentof lipid deposition.