Endocrine Abstracts (2002) 3 OC6

Y chromosome consomic strains and metabolic syndrome in the stroke prone spontaneously hypertensive rat

P Strahorn1, D Graham2, L Crawford2, JJ Morton1, N Sattar2 & AF Dominiczak1

1BHF Blood Pressure Group, Department of Medicine and Therapeutics, Royal Infirmary, University of Glasgow, Glasgow, UK; 2Department of Clinical Biochemistry, Royal Infirmary, University of Glasgow, Glasgow, UK.

Objective: The spontaneously hypertensive stroke prone rat (SHRSP) is a model of insulin resistance and dyslipidemia. Feeding a 60% fructose diet exaggerates these phenotypes. It has been suggested that the Y chromosome may influence lipid levels in the spontaneously hypertensive rat (SHR). Therefore we examined the effects of Y chromosome on lipid phenotypes in the SHRSP after fructose feeding.

Design and Methods: The S.W. Y consomic strain was constructed by introgressing the Y chromosome of the WKY strain into the recipient SHRSP strain, similarly the reciprocal W.S. Y strain was constructed. At 12 week of age S.W. Y (n=6), W.S. Y (n=6), SHRSP (n=9) and WKY (n=9) were fed 60% fructose diet for 14 days. Tail cuff blood pressure, blood glucose, body weight and left ventricular hypertrophy (by echocardiography) were measured before and after fructose feeding. At sacrifice lipid profile including plasma triglycerides (TG), total cholesterol (chol), HDL cholesterol and insulin was measured.

Results: Blood pressure (mmHg) was significantly different between WKY 128±3.8 and SHRSP 173±5.2*** and between WKY and WKY.SPGlaYs 148±5.7*. Weight gain (g) was significantly different between WKY 34.3±1.9 and SHRSP 26.8±1.1* and between WKY and WKY.SPGlaYs 22.5±2.4**. TG (mmol/L) differed significantly between WKY 1.7±0.2 and SHRSP 4.1±0.5***, as well as between SHRSP and SP.WKYGlaYw 2.6±0.4**. LVH(mg/g), Chol(mmol/L) and HDl (mmol/L) differed between WKY and SHRSP strains: 2.7±0.1 vs 3.4±0.1**, 2.6±0.1 vs 2.3±0.1* and 1.1±0.1 vs 1.8±0.1*** respectively (*p<0.05, **p<0.01, ***p<0.001). Insulin and glucose levels did not differ between groups.

Conclusion: Transfer of the Y chromosome from WKY to SHRSP was associated with significantly reduced plasma triglycerides. Transfer of the Y chromosome from SHRSP to WKY did not significantly affect circulating lipid levels, however blood pressure and weight gain were significantly affected. These consomic experiments implicate the Y chromosome in lipid metabolism, body mass and hypertension in the SHRSP.

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