ABSTRACT
AIM:To clarify the effects of high fat/cholesterol diet on lipid metabolism and atherogenesis in treble genes mutant mice.METHODS:ApoE-/-/LDLR-/-/Leprdb/db mice were generated by cross apolipoprotein E,lower density lipoprotein receptor gene knockout mice with leptin receptor gene spontaneous point mutants.The mice were fed with high fat/cholesterol diet from 22-day-old.The total plasma cholesterol(TC),triglyceride(TG)and glucose levels were measured and pathological changes of aorta intima and liver were analyzed.RESULTS:A significant elevated TC,TG and glucose levels in plasma with progress of time in young treble gene mutant mice were observed,which were higher than that in ApoE-/-/LDLR-/-and Leprdb/db mutants.At time of only 2 weeks after fed with high fat/cholesterol diet,TC and TG levels reached(106.75?3.40)mmol/L,(9.12?1.35)mmol/L,respectively in treble gene mutant mice,4.33-and 2.36-fold higher than those in treble genes mutants fed with normal chow diet.The levels were continuously increased until final experimental point.Intima of the aorta appeared with various injuries such as edema,desquamation of the endothelial cells,foam cell formation,rupture of IEL in local regions of root and arch areas of aorta at 2 weeks after fed with high fat/cholesterol diet.Microscopic pathological complex of significant local intima incrassation and fatty change of the liver were observed in the mutants that fed with high fat/cholesterol diet for 8 weeks.Injuries of aorta were severe than normal dietetic control group.CONCLUSION:High fat/cholesterol diet as a key dietary factor is significant aggravated lipid metabolism abnormity,promotes early damage of aorta and process of atherogenesis in the treble genes mutants.
ABSTRACT
5 fold) were noted.Six significant differential proteins in gel were identified by LTQ-ESI,e.g.endoplasmin precursor,acidic leucin-rich nuclear phosphoprotein 32 family member A,serotransferrin precursor,stress-70 protein precursor,fibronectin precursor,complement C3 precursor,fibrinogen gamma polypeptide.CONCLUSION: The protein profile of apoE-/-/LDLR-/-mouse liver exhibits significant difference compared to that of WT mice.The results imply that lipid metabolism relative polygenetic mutation contributes to the alteration of mouse liver protein expression profile,especially that lipid metabolism related perhaps participates in dysfunction in lipid metabolism during atherogenesis.