TY - JOUR
T1 - Metabolic consequences of intermittent hypoxia
T2 - Relevance to obstructive sleep apnea
AU - Drager, Luciano F.
AU - Jun, Jonathan C.
AU - Polotsky, Vsevolod Y.
N1 - Funding Information:
Luciano F. Drager and Jonathan Jun are Post-Doctoral Fellow at Johns Hopkins University. Dr. Drager is supported by the Conselho Nacional de Desenvolvimento Científico e Tecnológico ( CNPq # 200032/2009-7 ) and Fundação Zerbini , Brazil. Dr.Jun is supported by the National Sleep Foundation / American Lung Association Pickwick Grant ( SF-78568N ) and NIH T32 training grant ( HL07534 ).
Funding Information:
Vsevolod Y. Polotsky is supported by NIH ( R01 HL80105, 5P50HL084945 ) and the United States Israel Binational Science Foundation (grant BSF No. 2005265 ).
PY - 2010/10
Y1 - 2010/10
N2 - 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.
AB - 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.
KW - dyslipidemia
KW - insulin resistance
KW - intermittent hypoxia, obstructive sleep apnea
KW - metabolic syndrome
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U2 - 10.1016/j.beem.2010.08.011
DO - 10.1016/j.beem.2010.08.011
M3 - Review article
C2 - 21112030
AN - SCOPUS:78649517782
SN - 1521-690X
VL - 24
SP - 843
EP - 851
JO - Best Practice and Research: Clinical Endocrinology and Metabolism
JF - Best Practice and Research: Clinical Endocrinology and Metabolism
IS - 5
ER -