Increased IGF-1 bioavailability preserves cardiac function and protects against diet-induced increases of blood pressure in high-fat fed mice

Abstract

Purpose: Obesity is an established risk factor for cardiovascular disease, hypertension and left ventricular hypertrophy and is associated with a decline in plasma free IGF-I levels. This study evaluates the effect of high-fat feeding on cardiac and vascular function in mice with increased IGF-I bioavailability (IGFBP-1 knockout mice, BP1KO). Methods: Blood pressure was measured non-invasively after 8 and 16 weeks of feeding a 45% high fat diet. Cardiac structure and function was examined by echocardiography. Left ventricular and septum wall size was measured in systole and diastole. Doppler echocardiography measured mitral valve function. Mice were sacrificed and the heart and the left ventricle weighed. Results: After 8 and 16 weeks of high-fat feeding, BP1KO mice were protected against obesity-related hypertension (117.7 vs. 127 mmHg and 129.3 vs 143 mmHg BP1KO and WT respectively). At 16 weeks the left ventricular wall in systole was larger in the KO cohort, but stroke volume was preserved. At 24 weeks there was no difference in ventricular or septal wall measurements. Left ventricle to heart weight ratio was higher in the WT than the BP1KO mice (73.38% vs 69.20%). Mitral Valve Measurements Values expressed as mean±SEM. *p<0.05, **p<0.01. Conclusions: Increased IGF-1 bioavailability protected against the rise in blood pressure observed in obesity. Although there was no difference in ventricular wall thickness, the WT controls exhibited left ventricular hypertrophy in comparison to the BP1KO group. IGF-1 was shown to ameliorate high-fat diet induced cardiac dysfunction. Decreased E/A ratio, increased IVRT and IVCT, measures of diastolic dysfunction, were preserved in the BP1KO cohort. Our data shows that increased IGF-1 bioavailability protects against the cardiac dysfunction, left ventricular hypertrophy and hypertension normally associated with caloric excess.