The Effects Of LRTG On The Hyperlipidemia Hamsters And TG-lowering Mechanism

In the present,the lipid changes were observed by comparing hamsters in feeding differents formulation diets,choosing for the better fat diet recipes to form a more stable hyperlipideamia model with hypertriglyceridemia characteristics.The molecular mechanisms of TG metabolism were detected by molecular biology techniques.Take advantage of the model of hyperlipidemia in hamsters,evaluating the hypolipidemic effect of LRTG in reducing serum and hepatic lipids levels and exploring the mechanisms of its triglyceride-lowering effect by determining the mRNA expressions of the enzymes,proteins and receptors that involved in triglyceride metabolism.It provides a scientific basis for the development of effective drugs in triglyceride-lowering.Hamsters were assigned randomly to groups of control,model I and model II groups,Animals of the control group was fed with the normal diets.The model I and model II groups were fed with different high-fat diets respectively for four weeks.The food intake,body weight and serum lipids(TG,TC,LDL-C and HDL-C)of hamsters were measured every week during the experiment.The hepatic levels of TG,TC were examined after four weeks.The relative expression changes of AMPK,SREBP-1c,ACC,SCD-1,CPT-1,PPARa,AGPAT2,DGAT2,MTTP,ApoB and LPL mRNA in liver were tested by real-time PCR.Hamsters were assigned randomly to groups of control,hyperlipidemia model,positive control(fenofibrate 0.15g/kg)and high(1.2g/kg),middle(0.6g/kg),low(0.3g/kg)doses of LRTG respectively.Animals of the control groups were fed with the normal diets,the rest were fed with the high-fat diets.After One week,the blood samples were collected for the estimation of secrum TG,TC,LDL-C and FFA used to determine the formation of hyperlipidemia.A week later,the groups treated were intragastrically administrated with drugs according to the prescribed dosage respectively for three weeks.The hypolipidemic effect of LRTG was evaluated through detecting the serum lipids(TC,TG,LDL-C and FFA),hepatic lipids(TC,TG)concentrations,serum LPL and hepatic HL activities.The real-time PCR was used to screen the triglyceride-lowering targets.the protein expressions of hepatic AMPK,SREBP-1c,Phospho-AMPK and Phospho-SREBP-1c were detected by western blot.The experimental results showed that the levels of serum TG,TC and LDL-C bedan to increase and maintain until the end of experiment during the hamsters in model I were induced by high-fat diet for 4 weeks;high-fat feed formulation in model ? is insufficient to form a stable hypertriglyceridemia.The TG metabolism mechanism research indicated that the hepatic AMPK mRNA expression in the model group was lower than in the control group,the expressions of SREBP-lc,SCD-1,ACC in the model were higher,which is most likely due to a increase in fatty acid synthesis in the liver;Meanwhile,the downregulatings of PPARamRNA and inhibiting the activity of its downstream target enzyme CPT-1,which is most likely due to a decrease in the P-oxidation of fatty acids;AGPAT2,DGAT2 genes upregulated,promoting hepaticTG synthesis;These factors together caused TG metabolism.The results about lipid-lowering effect of LRTG indicated that the hamsters fed a high fat diet were treated with any of the three LRTG dosages and fenofibrate for three weeks significantly decreased the levels of serum TG,TC,LDL-C,FFA.Moreover,hepatic TG,TC concentrations were also reduced,the data suggested that LRTG was more potent in decreasing serum TG.Its triglyceride-lowering mechanism studies showed that LRTG significantly enhanced the levels of the activated form of AMPK and promoted the phosphorylation of sterol regulatory element binding protein-1 c and inhibited the activities of SREBP-1c and its downstream targets,such as SCD-1,GPAT,DGAT2,which is most likely due to a decrease in fatty acid and triglyceride synthesis in the liver.LRTG also inhibited AGPAT2 activity,further reducing the TG synthesis.A significant decrease in ApoCIIImRNA and increase in LPLmRNA expressions in liver after LRTG supplementation was observed in our study,which is most likely due to a decrease in triglyceride synthesis in serum via the downregulating of ApoCIIImRNA and promoting LPLmRNA.Therebefore,LRTG is an effective drug in triglyceride-lowering.