Metabolic consequences of intermittent hypoxia: relevance to obstructive sleep apnea.
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.
Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Johns Hopkins Asthma and Allergy Center, 5501 Hopkins Bayview Circle, Baltimore, MD 21224, USA.
Luciano F
LF
Drager
Jonathan C
JC
Jun
Vsevolod Y
VY
Polotsky
D000818:Animals; D004195:Disease Models, Animal; D005947:Glucose / Q000378:metabolism; D006801:Humans; D000860:Hypoxia / Q000150:complications* / Q000378:metabolism*; D050356:Lipid Metabolism / Q000502:physiology; D051379:Mice; D008954:Models, Biological; D010507:Periodicity; D020181:Sleep Apnea, Obstructive / Q000150:complications* / Q000378:metabolism*
D005947:Glucose