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Effects of leptin deficiency on the development of respiratory control in mice
Author(s) -
Bierman Alexis,
Huang Kewu,
Mitzner Wayne,
Tankersley Clarke G.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1214-a
Subject(s) - medicine , hypercapnia , ventilation (architecture) , respiratory minute volume , endocrinology , tidal volume , obesity , respiratory system , apnea , mechanical engineering , engineering
Obesity in children and adults is a public health concern with potentially serious respiratory consequences, including asthma, hypoventilation, and sleep apnea. Previous studies revealed substantial respiratory dysfunction in adult leptin deficient (C57BL/6J‐Lep ob ) mice. In the current study, we tested the genetic influence of the ob allele on the development of breathing control and metabolism using wild type ( +/+ ) and homozygous ( ob/ob ) mice grouped by age: 2‐wks (lung development is incomplete; obesity is absent), and 10‐wks (lung development is complete; obesity is advanced in ob/ob mice). Oxygen consumption (VO 2 ) was measured immediately before determining breathing frequency ( f ) and tidal volume (V T ) in room air using whole‐body plethysmography. Breathing characteristics were also assessed during 5‐min hypercapnic (5% CO 2 ) and hypoxic (10% O 2 ) challenges. In room air, minute ventilation (V E = f x V T , in ml/min; ±SD) was significantly (P<0.05) elevated for +/+ compared with ob/ob (27.9±7.3 vs. 13.3±8.4) mice at 2‐wks of age. These results were largely a result of lower f observed in 2‐wk old ob/ob mice. By 10‐wks, V E was significantly (P<0.01) elevated in both groups (49.1±15.1 vs. 42.1±16.0), but the difference between +/+ and ob/ob mice was eliminated. Although both genotypic groups showed elevated hypoxic and hypercapnic V E responses (P<0.01) with age, ob/ob mice showed a depressed V E response (P<0.05) with hypercapnia at 2‐ and 10‐wks of age. A single linear relationship between V E (in room air) and VO 2 was found to characterize all mice, regardless of age or genotype, demonstrating a constant ventilatory equivalent (the ratio of V E to VO 2 ). In conclusion, leptin deficiency during development of respiration affects hypercapnic ventilatory depression without altering coupling between ventilation and metabolism.