PULMONARY VENTILATION AND MECHANICS IN MORBIDLY OBESE ZUCKER RATS

The obese Zucker rat, an autosomally genetic model of obesity, represents a good model of relatively early onset human obesity. Although factors associated with the control of metabolism and thermoregulation have been studied extensively in these animals, pulmonary mechanics and ventilation have not been documented and form the basis of this investigation. Studies were carried out in 16 obese and 18 lean female littermates (698 +/- 79 versus 304 +/- 24 g, p < 0.001). Pulmonary function, including lung volumes and respiratory system compliance, was evaluated in supine anesthetized animals. With the exception of residual volume, all other lung volumes, including function residual capacity, total lung capacity, expiratory reserve volume, and inspiratory capacity, were significantly reduced (p < 0.05 or better) in the obese phenotype compared with volumes in the lean littermates. Pressure-volume relationships of the intact respiratory system and the excised lung were also determined. Although lung compliance was similar between the phenotypes, respiratory system compliance was significantly lower (0.85 +/- 0.06 versus 0.67 +/- 0.09 ml/cm H2O, p < 0.01) in the obese rats. Oxygen consumption and ventilatory parameters (including respiratory rate, tidal volume, minute ventilation, inspiratory time, and expiratory time) were similar between phenotypes breathing room air, and the minute ventilation in response to hypoxia was similar in both groups. In marked contrast, obese animals exhibited a blunted ventilatory response to hypercapnia (221 +/- 38 versus 135 +/- 44 ml/min, p < 0.01). In conclusion, many of the observations determined in this study are qualitatively similar to those previously described in morbidly obese human subjects, and therefore the obese Zucker rat may prove to be a useful animal model of simple obesity in human subjects.