Introduction
Leptin, an endocrine product of the ob gene, influences energy metabolism and autonomic nervous regulation. Recent evidence also suggests that leptin modifies respiratory control mechanisms. In humans, leptin is primarily secreted by adipocytes, and plasma leptin levels positively increase with body weight in obese individuals. Therefore, we hypothesize that leptin dysfunction has a critical role in respiratory complications associated with obesity.
Methods
Over a series of studies, lung function and structure were explored using leptin-deficient (ob) and leptin receptor-deficient (db) mice. Age-dependent changes in eupneic and hypercapnic ventilatory responses were measured using whole-body plethysmography. Quasistatic pressure-volume manuevers characterized changes in lung growth and pulmonary mechanics. Histology was performed to determine if and where fat deposition occurred in lung parenchymal tissue.
Results
1. Both ob and db mice demonstrate a rapid, shallow eupneic breathing pattern.
2. Both ob and db mice demonstrate hypercapnic hypoventilation.
3. Both ob and db mice show attenuated age-dependent changes in lung volume and compliance.
4. Leptin replacement in ob mice prevents the ventilatory complications associated with obesity and promotes lung growth.
5. In untreated ob mice, histological sections reveal fat deposition in the lung parenchyma, which is juxtaposited between airway and adjacent blood vessels.
Conclusions
Leptin appears to play a crucial role in normal lung structure and function. In the face of leptin deficiency or leptin receptor dysfunction, respiratory complications associated with obesity involve altered control of ventilation and pulmonary mechanics. In addition, lung growth and development appear to be impaired, and fat deposition occurs in the lung parenchyma. In conclusion, the results in this genetic model of obesity suggest that leptin regulation is essential to the development of respiratory control mechanisms.
References
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2. Tankersley, C.G., et al. 1998, J. Appl. Physiol. 85(6): 2261-2269.
3. O'Donnell, C.P., et al. 1999, Am. J. Resp. Crit. Care Med. 159: 1477-1484.