title: Systemic leptin produces a long-lasting increase in respiratory motor output in rats.
abstract: Leptin decreases food intake and increases energy expenditure. Leptin administration into the CNS of mice or rats increases alveolar ventilation and dysfunction in leptin signaling has been implicated in the hypoventilation that can accompany obesity. An increase in CO(2) chemosensitivity has been implicated in this response but it is unclear whether ventilation is augmented when PCO(2) is maintained constant. We examined the effects of intravenous leptin to test the hypothesis that systemic leptin administration in isoflurane anesthetized, mechanically ventilated and vagotomized rats would lead to a sustained increase in respiratory motor output that was independent of changes in end-tidal PCO(2), body temperature or lung inflation pressure (an indicator of overall lung and chest wall compliance). In anesthetized Sprague-Dawley rats with end-tidal PCO(2), lung compliance and rectal temperature maintained constant, injection of a bolus of leptin (0.25 mg, 0.5 mg/ml, i.v.), followed over the next 1 h by the intravenous infusion of an additional 0.25 mg, elicited a progressive increase in the peak amplitude of integrated phrenic nerve discharge lasting at least 1 h beyond the end of the infusion. The increase peaked at 90 min at 58.3 ± 5.7% above baseline. There was an associated increase in the slope of the phrenic response to increasing inspired CO(2). There was also a moderate and sustained decrease in arterial pressure 9 ± 1.3 mmHg at 120 min, with no associated change in heart rate. These data indicate that leptin elicits a sustained increase in respiratory motor output that outlasts the administration leptin via a mechanism that does not require alterations in arterial PCO(2), body temperature, or systemic afferent feedback via the vagus nerves. This stimulation may help to prevent obesity-related hypoventilation.
authors: Department of Physiology, Feinberg School of Medicine, Northwestern University Chicago, IL, USA.
authors: Zheng
authors: Z
authors: Chang
authors: Edmund
authors: E
authors: Ballou
authors: Weijie
authors: W
authors: Jiao
authors: Kevin E
authors: KE
authors: McKenna
authors: Shaun F
authors: SF
authors: Morrison
authors: Donald R
authors: DR
authors: McCrimmon
keywords: leptin; leptin stimulation of breathing; metabolic control of breathing; neural control of breathing; respiratory modulation