Metabolic consequences of sleep-disordered breathing

Jonathan Jun, Vsevolod Y. Polotsky

Research output: Contribution to journalArticlepeer-review

79 Scopus citations

Abstract

There is increasing evidence of a causal relationship between sleep-disordered breathing and metabolic dysfunction. Metabolic syndrome (MetS), a cluster of risk factors that promote atherosclerotic cardiovascular disease, comprises central obesity, insulin resistance, glucose intolerance, dyslipidemia, and hypertension, manifestations of altered total body energy regulation. Excess caloric intake is indisputably the key driver of MetS, but other environmental and genetic factors likely play a role; in particular, obstructive sleep apnea (OSA), characterized by intermittent hypoxia (IH), may induce or exacerbate various aspects of MetS. Clinical studies show that OSA can affect glucose metabolism, cholesterol, inflammatory markers, and nonalcoholic fatty liver disease. Animal models of OSA enable scientists to circumvent confounders such as obesity in clinical studies. In the most widely used model, which involves exposing rodents to IH during their sleep phase, the IH alters circadian glucose homeostasis, impairs muscle carbohydrate uptake, induces hyperlipidemia, and upregulates cholesterol synthesis enzymes. Complicating factors such as obesity or a high-fat diet lead to progressive insulin resistance and liver inflammation, respectively. Mechanisms for these effects are not yet fully understood, but are likely related to energy-conserving adaptations to hypoxia, which is a strong catabolic stressor. Finally, IH may contribute to the morbidity of MetS by inducing inflammation and oxidative stress. Identification of OSA as a potential causative factor in MetS would have immense clinical impact and could improve the management and understanding of both disorders.

Original languageEnglish (US)
Pages (from-to)289-306
Number of pages18
JournalILAR journal
Volume50
Issue number3
DOIs
StatePublished - 2009

Keywords

  • Diabetes
  • Intermittent hypoxia
  • Metabolic syndrome
  • Metabolism
  • Obesity
  • Risk factor
  • Rodent model
  • Sleep apnea

ASJC Scopus subject areas

  • Animal Science and Zoology
  • General Biochemistry, Genetics and Molecular Biology

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