Lung Surfactant Disaturated Phosphatidylcholine and Surfactant Proteins A and B in Dietary-Induced Obesity in Immature Rats † 1625

Abstract

Dietary-induced obesity in young rats is associated with increases in body weight and the fat pad weight/body weight ratio (a measure of obesity) and decreases in alveolar surface area per alveolar volume (Inselman, et al.JAP 1988;65:2291). A reduction in dynamic lung compliance also occurs. The present study investigated the effect of dietary-induced obesity on disaturated phosphatidyl-choline (DSPC) and surfactant proteins A (SP-A) and B (SP-B) levels. Newborn rats raised in litters of 4 pups/dam were fed a high fat diet post-weaning (obese group, O). A control group (C) consisted of newborn rats raised in litters of 14 pups/dam which were fed a normal rat diet after weaning. Male rats (O=13, C=21) were killed at age 8 weeks, and the lungs were perfused until visibly blood-free. The lungs were then lavaged with normal saline to recover bronchoalveolar lavage fluid, which was separated into large and small aggregates of surfactant by differential centrifugation. The lipid extracts of large and small aggregates of surfactant and lavaged lung tissue were treated with osmium tetroxide, and DSPC was quantified following chromatography on neutral alumina columns. Western blot analyses were performed for SP-A and SP-B on the large aggregates and lung homogenates. Obesity in O animals was confirmed by increases in body weight (24%, P<0.001) and the fat pad weight/body weight ratio (359%, P<0.001) when compared with C animals. When compared with the C group, DSPC in the O rats was elevated by 28% in the lung [O: 177±6; C: 138±4 μg phospholipid phosphorus (PLPi/)/lung] (mean±SE) (P<0.0001), 15% in the large aggregates (O: 17.6±0.8; C: 15.3±0.7 μg PLPi/lung)(P<0.05) and 35% in the small aggregates (O: 8.9±0.8; C: 6.6±0.4 μg PLPi/lung) (P<0.01). SP-A and SP-B levels were increased in large aggregates of surfactant in O rats but not in lung tissue. In addition, surfactant SP-A and SP-B were elevated in O animals when compared with C animals, while lung tissue SP-A and SP-B levels were similar between the two groups. These observations indicate that this model of obesity results in changes in synthesis and secretion of surfactant proteins and phospholipids. These studies suggest that additional factors may be responsible for the alterations in lung function since increased levels of surfactant proteins and phospholipids are insufficient to improve dynamic lung compliance in immature rats rendered obese by dietary changes.