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1 Medicine, Johns Hopkins University, Baltimore, Maryland, United States
2 medicine, Johns Hopkins University, Baltimore,, Maryland, United States; Medicine, Johns Hopkins University, Baltimore, Maryland, United States
3 Medicine, University of Pittsburgh, Pittsburg, Pennsylvania, United States
* To whom correspondence should be addressed. E-mail: vpolots1{at}jhmi.edu.
Obstructive sleep apnea (OSA) is characterized by chronic intermittent hypoxia (CIH) and associated with dysregulation of lipid metabolisms and atherosclerosis. Causal relationships between OSA and metabolic abnormalities have not been established due to confounding effects of underlying obesity. The goal of the study was to determine if CIH causes lipid peroxidation and dyslipidemia in the absence of obesity, and whether the degrees of dyslipidemia and lipid peroxidation depend on the severity of hypoxia. Lean C57BL/6J mice were exposed to CIH for 4 wks with a FIO2 nadir of either 10% (moderate CIH) or 5% (severe CIH). Mice exposed to severe CIH exhibited significant increases in fasting serum levels of total cholesterol (129 ± 2.9 mg/dl vs. 113 ± 2.8 mg/dl in control mice, p < 0.05) and LDL-C (85.7 ± 8.9 mg/dl vs. 56.4 ± 9.7mg/dl, p < 0.05) in conjunction with a 1.5-2 fold increase in lipoprotein secretion, and up-regulation of hepatic stearoyl coenzyme A desaturase 1 (SCD-1). Severe CIH also markedly increased lipid peroxidation in the liver (malondialdehyde levels of 94.4 ± 5.4 nmol/mg vs. 57.4 ± 5.2 nmol/mg in control mice (p < 0.001). In contrast, moderate CIH did not induce hyperlipidemia or change in hepatic SCD-1 levels, but did cause lipid peroxidation in the liver at a reduced level relative to severe CIH. In conclusion, CIH leads to hypercholesterolemia and lipid peroxidation in the absence of obesity, and the degree of metabolic dysregulation is dependent on the severity of the hypoxic stimulus.
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