Leptin attenuates respiratory complications associated with the obese phenotype

A profile of respiratory complications has been associated with the onset a nd development of obesity in humans. Similar phenotypes have been routinely demonstrated in genetic animal models of obesity such as the ob mouse (C57 BL/6J-Lep(ob)). The objective of the present study was to test the hypothes is that a constellation of respiratory complications are attenuated with le ptin (i.e., protein product of the ob gene) replacement. Daily leptin admin istration during a 6-wk period was conducted to control body weight of muta nt ob mice similar to genotypic control groups. During the treatment period , repeated baseline ventilatory measurements were assessed by using whole b ody plethysmography while quasistatic pressure-volume curves were performed to further explore the role of leptin in improving lung mechanics. Diaphra gmatic myosin heavy chain (MHC) isoform phenotype was examined to determine proportional changes in MHC composition. In room air, breathing frequency and minute ventilation were significantly (P < 0.01) different among ob tre atment groups, suggesting that leptin opposed the development of a rapid br eathing pattern observed in vehicle-treated ob mice. Quasistatic deflation curves indicated that the lung volume of leptin-treated ob mice was signifi cantly (P < 0.05) greater relative to vehicle-treated ob mice at airway pre ssures between 0 and 30 cmH(2)O. Diaphragm MHC composition of leptin-treate d ob mice was restored significantly (P < 0.05) to resemble the control phe notype. In this genetic mouse model of obesity, the results suggested that respiratory complications associated with the obese phenotype, including ra pid breathing pattern at baseline, diminished lung compliance, and abnormal respiratory muscle adaptations, are attenuated with prolonged leptin treat ment.