Cardiac hypertrophy and oxidative metabolism in novel congenic leptin receptor deficient BBDR.cg‐lepr.cp rats (1155.10)

Abstract

Congenic BBDR.cg‐lepr.cp rats generated by introgression of the Koletsky leptin receptor mutation into the BioBreeding Diabetes Resistant (BBDR) rat develop obesity and diabetes mellitus, known risk factors for heart failure. Here we studied cardiac function and myocardial oxidative metabolism in these rats by non‐invasive imaging. Myocardial glucose utilization (18F‐fluorodeoxyglucose uptake) and oxygen consumption (washout constant for 11C‐acetate derived from monoexponential fitting) were measured by positron emission tomography (PET); left ventricle (LV) mass, systolic function and cardiac output by echocardiography. Compared with non‐diabetic littermates, diabetic rats were obese (body weight 463±36 vs. 706±65 g, p<0.01), hyperglycemic (6±1 vs. 22±10 mM, p<0.01), had elevated blood pressure (136±5 vs. 151±13 mmHg, p=0.02), comparable systolic function (fractional shortening 49 vs. 48%), but higher LV mass (0,6±0,1 vs. 0,9±0,1 g, p<0.01). Diabetic rats had lower fasting myocardial glucose uptake (p=0.04) and lower efficiency of myocardial forward work (LV work / oxygen consumption * myocardial mass; 69000±8000 vs. 54000±12000 mmHg L/min; p=0.03), despite having comparable resting myocardial oxygen consumption in fasting state. Results suggest that BBDR.cg‐lepr.cp rats should prove a useful new model to study the adverse effects of obesity and diabetes on cardiac metabolism.Grant Funding Source: Supported by: VR 2011‐3900; EFSD, SSMF, the SUMMIT consortium (IMI‐2008/115006).