Modified control of breathing in genetically obese (ob/ob)
mice.
Tankersley, Clarke, Steven Kleeberger, Bradley Russ, Alan Schwartz,
and Philip Smith.
Departments of Environmental Health Sciences, and Pulmonary and
Critical Care Medicine, The Johns Hopkins Medical Institutions,
Baltimore, MD 21205
APStracts 3:0172A, 1996.
Attenuated hypercapnic chemosensitivity and hypoventilation are
characteristics periodically associated with human obesity. We tested
the hypothesis that ventilatory control is altered by genetic
determinants and age-dependent factors which influence the obese
phenotype. To this end, the magnitude and pattern of breathing were
examined prior to and associated with the development of obesity in
C57BL/6J mice homozygous and heterozygous at the ob gene locus.
Breathing frequency and tidal volume were measured using whole body
plethysmography, and minute ventilation was assessed during acute
hypoxic and hypercapnic challenges with intermittent room air
exposures. In age- and weight-matched mice prior to pronounced
obesity, significant (P < 0.05) reductions in hypercapnic
ventilatory sensitivity occurred in mutant (ob/ob) mice relative to
wild-type (+/+) homozygotes due primarily to an attenuated tidal
volume. Longitudinal studies indicated that mutant ob mice developed
rapid baseline breathing relative to the wild-type accompanying a
two-fold greater increase in body mass. Early differences between
homozygotes in hypercapnic ventilatory sensitivity were maintained
through 230 d. These data demonstrate that genetic determinants at or
closely linked to the ob locus influence hypercapnic ventilation
prior to the emergence of pronounced obesity while changes in
baseline breathing appear due to age-dependent increases in body
weight.
Received 13 November 1995; accepted in final form 12 March 1996.
APS Manuscript Number A1192-5.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 1 April 96