Apolipoprotein D in Lipid Metabolism and Its Functional Implication in Atherosclerosis and Aging

Dyslipidemia is characterized by increased triglyceride and low-density lipoprotein (LDL) levels, and decreased high-density lipoprotein (HDL) levels. Such an atherogenic lipid profile often predisposes an at risk individual to coronary artery disease with incompletely understood mechanisms. Apolipoprotein D (apoD) is an atypical apolipoprotein. Unlike canonical apolipoproteins that are produced mainly in liver and intestine, apoD is expressed widely in mammalian tissues. ApoD does not share significant degrees of homology in amino acid sequence with other apolipoproteins. Instead, apoD is structurally similar to lipocalins, a diverse family of lipid-binding proteins that are responsible for transporting lipids and other small hydrophobic molecules for metabolism. Plasma ApoD is present mainly in HDL and to a lesser extent in low density lipoproteins (LDL) and very low-density lipoproteins (VLDL). Genetic variants of apoD are associated with abnormal lipid metabolism and increased risk of developing metabolic syndrome. Increased apoD deposition is detectable in atherosclerotic lesions of humans with established cardiovascular disease as well as mice with premature atherosclerosis. Moreover, apoD is associated with anti-oxidation and anti-stress activities, contributing to lifespan expansion in fruit flies. Elderly subjects and patients with Alzheimer exhibit markedly elevated apoD production in the brain. Thus, apoD is emerged as a significant player in lipid metabolism and aging. Here we focus our review on recent advances toward our understanding of apoD in lipid metabolism and address whether apoD dysregulation contributes to the pathogenesis of dyslipidemia and atherosclerosis. We will also discuss the functional implication of apoD in aging.