Developmental and metabolic implications of the hypoxic ventilatory response.
This review explores the evidence to support the leading hypothesis that the metabolic response to hypoxia early in life provides the pathophysiological basis for the metabolic syndrome. Hypoxia is a frequent occurrence during early development and induces a state of energy depletion that triggers a wide range of 'metabolic' responses to preserve homeostasis. Recent interest in the sequelae of energy depletion through hypoxic mechanisms has grown, particularly because of demonstrated links with ensuing metabolic abnormalities and increased risk for future cardiovascular disease. The 'metabolic syndrome' refers to the combination of obesity, hyperinsulinaemia, dyslipidaemia and hypertension in adults. The metabolic responses to energy depletion during early development provide explanations for some of the mechanisms that ultimately lead to serological features of metabolic dysfunction in children with sleep-disordered breathing. Thus, the acute compensatory response of energy conservation to hypoxia during early development at the cellular, serological and whole organism levels suggests that the metabolic abnormalities that develop later in life may in fact originate very early in life; in other words, constitute early life antecedents of adult disease. Evidence regarding the circumstances under which responses to hypoxia become maladaptive will be discussed, with a focus on chronic conditions and those associated with intermittent respiratory dysfunction such as sleep-disordered breathing.
Department of Medicine, The University of Sydney, NSW, Australia. kaw@med.usyd.edu.au
Karen
K
Waters
David
D
Gozal
D006801:Humans; D000860:Hypoxia / Q000150:complications / Q000196:embryology* / Q000378:metabolism*; D024821:Metabolic Syndrome / Q000209:etiology* / Q000503:physiopathology*