Metabolic consequences of intermittent hypoxia: Relevance to obstructive sleep apnea

Luciano F. Drager, Jonathan Jun, Vsevolod Polotsky

Research output: Contribution to journalArticle

Abstract

Obstructive sleep apnea (OSA) is recurrent obstruction of the upper airway leading to sleep fragmentation and intermittent hypoxia (IH) during sleep. There is growing evidence from animal models of OSA that IH is independently associated with metabolic dysfunction, including dyslipidemia and insulin resistance. The precise mechanisms by which IH induces metabolic disturbances are not fully understood. Over the last decade, several groups of investigators developed a rodent model of IH, which emulates the oxyhemoglobin profile in human OSA. In the mouse model, IH induces dyslipidemia, insulin resistance and pancreatic endocrine dysfunction, similar to those observed in human OSA. Recent reports provided new insights in possible mechanisms by which IH affects lipid and glucose metabolism. IH may induce dyslipidemia by up-regulating lipid biosynthesis in the liver, increasing adipose tissue lipolysis with subsequent free fatty acid flux to the liver, and inhibiting lipoprotein clearance. IH may affect glucose metabolism by inducing sympathetic activation, increasing systemic inflammation, increasing counter-regulatory hormones and fatty acids, and causing direct pancreatic beta-cell injury. IH models of OSA have improved our understanding of the metabolic impact of OSA, but further studies are needed before we can translate recent basic research findings to clinical practice.

Original languageEnglish (US)
Pages (from-to)843-851
Number of pages9
JournalBest Practice and Research: Clinical Endocrinology and Metabolism
Volume24
Issue number5
DOIs
StatePublished - Oct 2010

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Obstructive Sleep Apnea
Dyslipidemias
Insulin Resistance
Hypoxia
Glucose
Oxyhemoglobins
Sleep Deprivation
Lipolysis
Liver
Insulin-Secreting Cells
Airway Obstruction
Lipid Metabolism
Nonesterified Fatty Acids
Lipoproteins
Adipose Tissue
Rodentia
Sleep
Fatty Acids
Animal Models
Research Personnel

Keywords

  • dyslipidemia
  • insulin resistance
  • intermittent hypoxia, obstructive sleep apnea
  • metabolic syndrome

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

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abstract = "Obstructive sleep apnea (OSA) is recurrent obstruction of the upper airway leading to sleep fragmentation and intermittent hypoxia (IH) during sleep. There is growing evidence from animal models of OSA that IH is independently associated with metabolic dysfunction, including dyslipidemia and insulin resistance. The precise mechanisms by which IH induces metabolic disturbances are not fully understood. Over the last decade, several groups of investigators developed a rodent model of IH, which emulates the oxyhemoglobin profile in human OSA. In the mouse model, IH induces dyslipidemia, insulin resistance and pancreatic endocrine dysfunction, similar to those observed in human OSA. Recent reports provided new insights in possible mechanisms by which IH affects lipid and glucose metabolism. IH may induce dyslipidemia by up-regulating lipid biosynthesis in the liver, increasing adipose tissue lipolysis with subsequent free fatty acid flux to the liver, and inhibiting lipoprotein clearance. IH may affect glucose metabolism by inducing sympathetic activation, increasing systemic inflammation, increasing counter-regulatory hormones and fatty acids, and causing direct pancreatic beta-cell injury. IH models of OSA have improved our understanding of the metabolic impact of OSA, but further studies are needed before we can translate recent basic research findings to clinical practice.",
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AU - Jun, Jonathan

AU - Polotsky, Vsevolod

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