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The obese rat myocardial ectopic lipid signaling pathway change its significance

Author: WuHaoJie
Tutor: ZhangSuHua;ZhouBo
School: Chongqing Medical University
Course: Internal Medicine
Keywords: obesity myocardial lipid deposition cardiac function apoptosis protein kinase C(PKC) protein kinase B(PKB) glucose transporter 4(GLUT4) rosiglitazone myocardial ischemia reperfusion cardiac function
CLC: R589.2
Type: Master's thesis
Year: 2005
Downloads: 73
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Abstract


Objective To examine the effect of obesity on myocardial structure and function in high fat induced obese rats and study the effect of ectopic fat accumulation in myocardium on protein kinase C (PKC)and insulin signal cascade. Discuss the effect and mechanism of rosiglitazone intervention on myocardial abnormal alteration. Methods 24 male, 6 weeks age,Wistar rats, were assigned to two groups, obesity group(n=16)were fed with high fat food; control group(n=8)were fed with chow food. At the end of 10 week,half of obese group were randomly choosed to be fed with rosiglitazone( 3mg.kg-1.d-1, Rosi group) for 2 weeks, and the other animals were fed with saline as control. After 12 weeks follow-up, weight , body length, plasma biochemical parameters, hemodynamics were measured and then the animal were sacrificed for heart mass and abdomen fat, ultrastructure examination(electron microscope )and intramyocardial lipids. Apoptosis was identifid by terminal deoxynucleotidyl transferase-mediated dUTP nick end labling (TUNEL), and apoptosis index(AI) was obtained. Myocardial triglyceride(TG), diacylglycerol(DAG) were investigated by biochemical method. The expressions of nuclear factor κ B(NF-κB) and glucose transporter 4(GLUT4) were measured by immunohistochemical technique.The expression of PKC, protein kinase B(PKB/Akt) and GLUT4 protein were measured by western blotting. Results (1)In comparison with control group, weight, body length, Lee index, epididymal and retroperitoneal fat pad were incresed significantly in obese group, respectively. Accompanied with increased heart weight, left ventricular mass, decreased systolic and diastolic function. (2)In obese rats, plasma TG, free fatty acid(FFA) and fasting insulin(FINS) level were increased compared with control group;and myocardial TG, area percent of intramyocardial lipids, myocardial DAG were increased by 53%, 200%, 67%, respectively, compared with control group.but there was no significant difference in total cholesterol (TC),fasting blood glucose(FBG) and blood pressure between obese and control goups. (3)Cardiomyocytes AI were increased by 4.3 folds in obese rats in compared with control rats, Accompanied with upregulated PKC-ε of cytosol and membrane, NF-κ B level,and decreased expression of cytosolic PKB, GLUT4. (4)In comparison with obese group, abdomen fat, palama TG, FFA ,FINS, myocardial TG and DAG, intramyocardial lipids, translocate expression of PKC-ε, NF-κB level were decreased significantly. The expression of PKB/Akt and GLUT4 were increased. At the same time, AI were decreased by 67%, accompanied with improved cardiac systolic and diastolic function. Conclusion These results suggested that myocardial signal transduction pathways abonomality related to accumulation of intramyocardial lipid is critically involved in cardiac dysfunction ,cardiomyocyte apoptosis and hypertrophy,which is inhibited by peroxisome proliferator-activated receptor-γ dependent pathway.Objective To examine the effect of obesity on myocardial ischemia reperfusion and whether rosiglitazone contributes to protect heart against myocardial reperfusion injury in obese rats and discuss the latent mechanism. Methods 36 male, 6 weeks age, Wistar rats, were assigned to two groups, obesity group(n=24)were fed with high fat food; control group(n=12)were fed with chow food. At the end of 10 weeks,half of obese group were randomly choosed to be fed with rosiglitazone( 3mg?kg-1?d-1, Rosi group) for 2 weeks. Obese rats were fed with saline. At the end of 12 weeks, rats were subjected to 40 minutes of ischemia followed by 2 hour of reperfusion, and at the same time cardiac function' dissertation">cardiac function were measured. The animal were sacrificed and the heart were harvest for PKB/Akt and GULT4 western blotting, apoptosis .Other animals were used for ischemic and infarct area testing with Evans blue and TTC , respectively . Results Compared with control group, obese group were decreased in cardiac function , as well as increased apoptosis, ischemic and infarct area were extended . The relative protein contents

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CLC: > Medicine, health > Internal Medicine > Endocrine diseases and metabolic diseases > Metabolic diseases > Lipodystrophy
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