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Systemic leptin produces a long-lasting increase in respiratory motor output in rats.

Chang Z, Ballou E, Jiao W, McKenna KE, Morrison SF, McCrimmon DR - Front Physiol (2013)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, Feinberg School of Medicine, Northwestern University Chicago, IL, USA.

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.

No MeSH data available.


Related in: MedlinePlus

CO2 Response curves in leptin (n = 7) vs. control (n = 4) rats measured 2–2.5 h following the initial bolus injection of leptin. Three levels of CO2 were delivered via altering the fraction of CO2 in the inspired gas delivered via the ventilator. (A) Plot of the average phrenic nerve activity at each level of end-tidal PCO2. Responses were fit with a least squares regression for which the equations are shown. (B) Scatter plot of slopes of the individual CO2 responses obtained for each animal as well as the group means ± S.E.M. *P < 0.05. Horizontal error bars in (A) indicate differences in the end-tidal PCO2 for individual animals.
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Figure 3: CO2 Response curves in leptin (n = 7) vs. control (n = 4) rats measured 2–2.5 h following the initial bolus injection of leptin. Three levels of CO2 were delivered via altering the fraction of CO2 in the inspired gas delivered via the ventilator. (A) Plot of the average phrenic nerve activity at each level of end-tidal PCO2. Responses were fit with a least squares regression for which the equations are shown. (B) Scatter plot of slopes of the individual CO2 responses obtained for each animal as well as the group means ± S.E.M. *P < 0.05. Horizontal error bars in (A) indicate differences in the end-tidal PCO2 for individual animals.

Mentions: To test the aggregate sensitivity of central and peripheral chemoreceptors, a CO2 response curve was generated at the end of the experiment in both the leptin and control groups of animals. The average slope of the CO2 response curve in leptin treated rats (Figure 3; n = 7) was more than twice that of control animals (P < 0.05; n = 4).


Systemic leptin produces a long-lasting increase in respiratory motor output in rats.

Chang Z, Ballou E, Jiao W, McKenna KE, Morrison SF, McCrimmon DR - Front Physiol (2013)

CO2 Response curves in leptin (n = 7) vs. control (n = 4) rats measured 2–2.5 h following the initial bolus injection of leptin. Three levels of CO2 were delivered via altering the fraction of CO2 in the inspired gas delivered via the ventilator. (A) Plot of the average phrenic nerve activity at each level of end-tidal PCO2. Responses were fit with a least squares regression for which the equations are shown. (B) Scatter plot of slopes of the individual CO2 responses obtained for each animal as well as the group means ± S.E.M. *P < 0.05. Horizontal error bars in (A) indicate differences in the end-tidal PCO2 for individual animals.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3569609&req=5

Figure 3: CO2 Response curves in leptin (n = 7) vs. control (n = 4) rats measured 2–2.5 h following the initial bolus injection of leptin. Three levels of CO2 were delivered via altering the fraction of CO2 in the inspired gas delivered via the ventilator. (A) Plot of the average phrenic nerve activity at each level of end-tidal PCO2. Responses were fit with a least squares regression for which the equations are shown. (B) Scatter plot of slopes of the individual CO2 responses obtained for each animal as well as the group means ± S.E.M. *P < 0.05. Horizontal error bars in (A) indicate differences in the end-tidal PCO2 for individual animals.
Mentions: To test the aggregate sensitivity of central and peripheral chemoreceptors, a CO2 response curve was generated at the end of the experiment in both the leptin and control groups of animals. The average slope of the CO2 response curve in leptin treated rats (Figure 3; n = 7) was more than twice that of control animals (P < 0.05; n = 4).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, Feinberg School of Medicine, Northwestern University Chicago, IL, USA.

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.

No MeSH data available.


Related in: MedlinePlus