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Abstract - Obesity has been described as a state of chronic oxidative stress. There are several ways in which obesity directly affects the cardiovascular system. -The klotho gene functions as an aging -suppressor gene that protects cells and tissues from oxidative stress. - Its now well known that Exercise and or antioxidants can prevents oxidative damage by reducing oxidative stress. -This study was carried out in order to clarify the effects of exercise and/or antioxidants on klotho gene messenger RNA expression during oxidative stress and its effects on cardiac tissue. -The animals were divided into 5 groups with group II subdivided into 2 subgroups. The group I is the negative control group who received balanced diet in which fat represents12% of the total caloric requirement for 16 weeks. Group II is the positive control and subdivided into group IIa who received high fat diet- in which the fat represents 60% of the total caloric requirement- for 16 weeks, group IIb who received high fat diet for 24weeks, group III received high fat diet for 24 weeks then were submitted for exercise for 45 minutes /day for the last 8 weeks. Group IV received high fat diet for 24 weeks then received vitamin E at a dose of 1gm/kg for the last 8 weeks and group V received high fat diet for 24 weeks then undergone exercise training for 30-45 minutes /day and received vitamin E at a dose of 1gm/kg for the last 8 weeks. -The parameters used to evaluate the oxidative stress were serum insulin level, serum glucose level, HOMA, serum total cholesterol and TG and TNF expression level in cardiac tissue using RT-PCR. Expression of klotho gene was detected in the kidney using RT-PCR. -The obtained results of this study could be summarized as follow: -The consumption of high fat diet -in which the fat represents 60% of the total caloric requirements- by the rat for 16 and 24 weeks resulted in a significant increase in weight associated with insulin resistance manifested by a significant increase in serum insulin levels, serum glucose level and HOMA and dyslipidemia manifested by significant increase in serum total cholesterol and TG and significant increase in TNF expression in cardiac tissue and also was associated with significant decrease in klotho gene expression in the kidney on comparing them with the control group. - Exercise training for 45 minutes /day for 8 weeks resulted in a significant improvement in the insulin resistance state regarding serum insulin, serum glucose and HOMA and improvement in dyslipidemia manifested by significant decrease in serum total cholesterol and TG, also it was associated with significant decrease in TNF expression level in cardiac tissue and significant increase in expression of klotho gene in the kidney on comparing them with the control group received only high fat diet. - Antioxidant treatment for 8 weeks resulted in a significant improvement in the insulin resistance state regarding plasma glucose and HOMA with statistically nonsignificant decrease in plasma insulin and TNF expression level in cardiac tissue, and significant decrease in serum total cholesterol and TG, also, it was associated with significant increase in klotho gene expression level in the kidney on comparing them with the control group received only high fat diet. - Combined exercise training for 45 minutes /day with vitamin E treatment for 8 weeks resulted in a significant improvement in the insulin resistance state regarding serum insulin, serum glucose and HOMA and significant improvement in dyslipidemia also, it was associated with significant decrease in TNF expression level in cardiac tissue and significant increase in expression of klotho gene in the kidney on comparing them with the control group received only high fat diet. -By comparing the different parameters in the exercise group with that of the antioxidant group it was found that the body weight, insulin resistance parameters and TNF expression in cardiac tissue was significantly lower in the exercise group compared to the antioxidant group, while klotho mRNA expression was significantly higher in the antioxidant group compared to the exercise group. However regarding serum total cholesterol and TG no significant difference was detected between the two groups. -On comparing the different parameters in the exercise group with that of the exercise and antioxidant group the body weight and serum glucose level was significantly lower in the exercise and antioxidant group compared to the exercise group, no significant difference was noticed between the two groups regarding serum insulin level, HOMA, serum total cholesterol and serum T On the other hand, the TNF expression level in cardiac tissue was significantly lower in the exercise group compared to the exercise and antioxidant group However the klotho mRNA expression in the kidney was significantly higher in the exercise and antioxidant group compared to the exercise group. -On comparing the different parameters in the Antioxidant group (group IV) with the exercise and antioxidant group, we find that the body weight, serum glucose, serum insulin and HOMA were significantly lower while the klotho m RNA expression in the kidney was significantly higher in the exercise and antioxidant group compared to the antioxidant group. TNF expression in cardiac tissue was significantly lower in the exercise and antioxidant group compared to the antioxidant group.No significant difference was detected between the two groups regarding total cholesterol and TG. -On studing the relationship between klotho gene expression and TNF-alpha gene expression in different groups. There was a significant –ve correlation between klotho gene expression and TNF-alpha gene expression in all groups. |