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 im portance of this single peptide is vividly demonstrated by the profound obe sity exhibited by the ob/ob mouse (C57BL/6J-Lep(ob)) which is unable to pro duce functional leptin. The measurement of respiratory function in the ob/o b mouse shows that the profound obesity is associated with impaired respira tory mechanics and depressed respiratory control, particularly during sleep . Longitudinal studies and leptin replacement studies in the ob/ob mouse in dicate 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 a ssociated with markedly elevated leptin levels. Human obesity, similar to o besity in wildtype mice, also causes an elevation in circulating leptin. Ho wever, unlike the tight relationship between obesity and elevated leptin pr esent in an inbred strain of wildtype mice, human obesity is associated wit h more variable leptin levels for a given degree of adiposity. Thus, the po ssibility exists that a relative deficiency in leptin, or a leptin resistan ce, may play a role in obesity-related breathing disorders such as obesity hypoventilation syndrome (OHS) or obstructive sleep apnea (OSA). (C) 2000 E lsevier Science B.V. All rights reserved.