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Delivery of In Vivo Acute Intermittent Hypoxia in Neonatal Rodents to Prime Subventricular Zone-derived Neural Progenitor Cell Cultures
Published on: November 2, 2015
Developmental and metabolic implications of the hypoxic ventilatory response
1Department of Medicine, The University of Sydney, NSW, Australia. kaw@med.usyd.edu.au
Insights
Early life hypoxia can trigger metabolic responses that may lead to metabolic syndrome later in life. These early adaptive changes, including energy conservation, may explain later metabolic dysfunction and cardiovascular disease risk.
Area of Science:
- Developmental Biology
- Metabolic Physiology
- Cardiovascular Health
Background:
- Hypoxia during early development is common and induces energy depletion.
- This energy depletion triggers metabolic responses to maintain homeostasis.
- Links between early hypoxia, metabolic abnormalities, and cardiovascular disease risk are increasingly recognized.
Purpose of the Study:
- To review evidence supporting the hypothesis that early life metabolic responses to hypoxia form the basis of metabolic syndrome.
- To explore the mechanisms linking early developmental hypoxia to later metabolic dysfunction.
- To discuss conditions where hypoxic responses become maladaptive, focusing on chronic and intermittent respiratory issues.
Main Methods:
- Literature review of studies investigating the link between early life hypoxia and metabolic syndrome.
- Analysis of evidence on metabolic responses to energy depletion during development.
- Examination of data on sleep-disordered breathing and metabolic dysfunction in children.
Main Results:
- Early life hypoxia induces compensatory metabolic responses for energy conservation.
- These responses can explain metabolic dysfunction observed in children with sleep-disordered breathing.
- Metabolic syndrome components (obesity, hyperinsulinaemia, dyslipidaemia, hypertension) may originate from early life antecedents.
Conclusions:
- Metabolic syndrome may have its origins in early life responses to hypoxia.
- Understanding these early life antecedents is crucial for preventing adult metabolic diseases.
- Chronic or intermittent hypoxia, such as in sleep-disordered breathing, may lead to maladaptive metabolic responses later in life.
Abstract:
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.
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