Chronic intermittent hypoxia significantly delayed triglyceride-rich lipoprotein clearance (AUC 461.7 vs 260.0 mmol×h) and induced a 5-fold decrease in adipose lipoprotein lipase activity in mice.
Does chronic intermittent hypoxia inhibit clearance of triglyceride-rich lipoproteins and inactivate adipose lipoprotein lipase in a mouse model of sleep apnoea?
Chronic intermittent hypoxia, a hallmark of sleep apnea, decreases triglyceride-rich lipoprotein clearance and inhibits lipoprotein lipase activity in adipose tissue, potentially contributing to atherogenesis.
Absolute Event Rate: 461.7% vs 260%
p-value: p=0.035
AIMS: Delayed lipoprotein clearance is associated with atherosclerosis. This study examined whether chronic intermittent hypoxia (CIH), a hallmark of obstructive sleep apnoea (OSA), can lead to hyperlipidaemia by inhibiting clearance of triglyceride rich lipoproteins (TRLP). METHODS AND RESULTS: Male C57BL/6J mice on high-cholesterol diet were exposed to 4 weeks of CIH or chronic intermittent air (control). FIO(2) was decreased to 6.5% once per minute during the 12 h light phase in the CIH group. After the exposure, we measured fasting lipid profile. TRLP clearance was assessed by oral gavage of retinyl palmitate followed by serum retinyl esters (REs) measurements at 0, 1, 2, 4, 10, and 24 h. Activity of lipoprotein lipase (LpL), a key enzyme of lipoprotein clearance, and levels of angiopoietin-like protein 4 (Angptl4), a potent inhibitor of the LpL activity, were determined in the epididymal fat pads, skeletal muscles, and heart. Chronic intermittent hypoxia induced significant increases in levels of total cholesterol and triglycerides, which occurred in TRLP and LDL fractions (P5-fold decrease in LpL activity (P< 0.01) and an 80% increase in Angptl4 mRNA and protein levels in the epididymal fat, but not in the skeletal muscle or heart. CONCLUSIONS: CIH decreases TRLP clearance and inhibits LpL activity in adipose tissue, which may contribute to atherogenesis observed in OSA.
Drager et al. (2011) studied Obstructive sleep apnoea (mouse model) (n=79). Chronic intermittent hypoxia (CIH) vs. Chronic intermittent air (CIA) was evaluated on Area under the curve for retinyl esters (REs) concentrations (mmol × h) (p=0.035). Chronic intermittent hypoxia significantly delayed triglyceride-rich lipoprotein clearance (AUC 461.7 vs 260.0 mmol×h) and induced a 5-fold decrease in adipose lipoprotein lipase activity in mice.