Longitudinal micro-ultrasound assessment of the ob/ob mouse model: evaluation of cardiovascular, renal and hepatic parameters.

Abstract

Obesity is reaching epidemic proportions and is associated with increased risk factors for cardiovascular disease. Leptin-deficient mice (ob/ob) are widely employed to investigate obesity. Aim of this study was to provide a micro-ultrasound (μUS) longitudinal evaluation of the ob/ob mouse model in terms of cardiovascular effects, consequences for renal microcirculation and liver fat accumulation. Sixteen wild-type (wt) and eleven ob/ob male mice were studied at 8 (T₀) and 25 (T₁) weeks of age with a μUS system (Vevo2100) and B-mode and Doppler images were acquired. Cardiac output (CO), ejection fraction (EF), stroke volume (SV), fractional shortening (FS) and E/A ratio were measured from cardiac images. Mean diameter (Dm_abd, Dm_car), relative distension (relD_abd and relD_car) and pulse wave velocity (PWV_abd and PWV_car) were obtained for both abdominal aorta and common carotid. As regards renal microcirculation, renal resistivity and pulsatility index (RI and PI) were assessed. The ratio between grey levels related to liver and kidney (Steato-Score) was used as index of hepatic steatosis. At T₀, ob/ob mice showed reduced SV, EF, CO and relD_abd values and increased LVmass, PWV_abd, RI, PI and Steato-score measurements. The same comparison repeated at T₁ highlighted similar results for SV, EF, CO, RI, PI and Steato-Score; furthermore, obese mice showed reduced Dm_abd and Dm_car measurements in comparison with lean controls. The longitudinal analysis showed an increase in LVmass and Dm_abd and a reduction of FS, EF, CO, relD_abd and relD_car for wt animals, while no differences were found for the ob/ob group. ob/ob mice presented a premature cardiac dysfunction without a further age-related deterioration and a reduction in the abdominal aorta and carotid artery mean diameter in adult age. The proposed analysis can represent a valid approach for longitudinal studies aimed at testing new therapeutic strategies or for characterizing other mouse models.