Alan R. Schwartz

Leptin, obesity, and respiratory function

Leptin is a protein produced by adipose tissue that circulates to the brain and interacts with receptors in the hypothalamus to inhibit eating. The importance of this single peptide is vividly demonstrated by the profound obesity exhibited by the ob/ob mouse (C57BL/6J-Lep(ob)) which is unable to produce functional leptin. The measurement of respiratory function in the ob/ob mouse shows that the profound obesity is associated with impaired respiratory mechanics and depressed respiratory control, particularly during sleep. Longitudinal studies and leptin replacement studies in the ob/ob mouse indicate that leptin may act as both as a growth factor in the lung and as a neurohumoral modulator of central respiratory control mechanisms. Moreover, wildtype mice with diet-induced obesity have normal respiratory function associated with markedly elevated leptin levels. Human obesity, similar to obesity in wildtype mice, also causes an elevation in circulating leptin. However, unlike the tight relationship between obesity and elevated leptin present in an inbred strain of wildtype mice, human obesity is associated with more variable leptin levels for a given degree of adiposity. Thus, the possibility exists that a relative deficiency in leptin, or a leptin resistance, may play a role in obesity-related breathing disorders such as obesity hypoventilation syndrome (OHS) or obstructive sleep apnea (OSA).