Obstructive Sleep Apnoea and Lipid Metabolism: The Summary of Evidence and Future Perspectives in the Pathophysiology of OSA-Associated Dyslipidaemia

Abstract

Obstructive sleep apnoea (OSA) is associated with cardiovascular and metabolic comorbidities, including hypertension, dyslipidaemia, insulin resistance and atherosclerosis. Strong evidence suggests that OSA is associated with an altered lipid profile including elevated levels of triglyceride-rich lipoproteins and decreased levels of high-density lipoprotein (HDL). Intermittent hypoxia; sleep fragmentation; and consequential surges in the sympathetic activity, enhanced oxidative stress and systemic inflammation are the postulated mechanisms leading to metabolic alterations in OSA. Although the exact mechanisms of OSA-associated dyslipidaemia have not been fully elucidated, three main points have been found to be impaired: activated lipolysis in the adipose tissue, decreased lipid clearance from the circulation and accelerated de novo lipid synthesis. This is further complicated by the oxidisation of atherogenic lipoproteins, adipose tissue dysfunction, hormonal changes, and the reduced function of HDL particles in OSA. In this comprehensive review, we summarise and critically evaluate the current evidence about the possible mechanisms involved in OSA-associated dyslipidaemia.

Keywords: OSA; dyslipidaemia; lipid; metabolic dysfunction; obstructive sleep apnoea.

Figure 1

Overview of physiological lipoprotein metabolism. Apo—apolipoprotein; CE—cholesteryl ester; CM—chylomicron; HDL—high-density lipoprotein; HL—hepatic lipase; IDL—intermediate-density lipoprotein; LDLR—low-density lipoprotein receptor; LRP-1—LDL receptor-related protein 1; PL—phospholipid; TG—triglyceride; VLDL—very-low-density lipoprotein. For description and references, please see the text.

Figure 2

Overview of the main pathophysiological pathways in OSA-related dyslipidaemia. The red arrows show the altered pathways and dysregulations. CM—chylomicron; FFA—free fatty acid; HDL—high-density lipoprotein; HIF-1α—hypoxia-inducible factor 1 alpha; IR—insulin resistance; LDL—low-density lipoprotein; LDLR—low-density lipoprotein receptor; LpL—lipoprotein lipase; LRP-1—LDL receptor-related protein 1; oxLDL—oxidised-LDL; SCD-1—stearoyl-coenzyme A desaturase 1; SREBP-1—sterol regulatory element-binding protein 1; TG—triglyceride; VLDL—very-low-density lipoprotein. For description and references, please see the text.

Figure 3

(a) Antioxidant effects of HDL and LRP-1 and normal endothelial function; (b) impaired antioxidant mechanisms with consequential oxidative stress, inflammation and endothelial dysfunction in OSA. ABCA1—ATP-binding cassette transporter A1; ABCG1—ATP-binding cassette transporter G1; CD36—cluster determinant 36; CM—chylomicron; eNOS—endothelial nitric oxide synthase; HDL—high-density lipoprotein; IH—intermittent hypoxia; IL—interleukin; LDL—low-density lipoprotein; MMP—matrix metalloproteinase; NO—nitric oxide; oxLDL—oxidised-LDL; RCT—reverse cholesterol transport; ROS—reactive oxygen species; sLRP-1—soluble LDL receptor-related protein 1; Sr-A—macrophage scavenger receptor; SR-BI—scavenger receptor class B type I; VLDL—very-low-density lipoprotein. For description and references, please see the text.