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

Perdomo, German; Dong, H. Henry

Additional evidence of apoD function against oxidative stress stems from studies in fruit flies. Sanchez et al. [69] show that genetically modified Drosophila mutants with loss-of-function of the human apoD homolog gene (GLaz) exhibit high sensitivity to oxidative stress and nutrient deprivation. The GLaz mutant flies also have an increased accumulation of lipid peroxidation products in the body, accompanied by 10-15% reduction in lifespan. Conversely, Walker et al. [70] show that Drosophila with overexpression of the apoD homolog GLaz displays enhanced resistance to starvation and oxidative stress. ApoD overexpression also ameliorates lipid peroxidation with a 30% extension of lifespan in flies [70] . Similar observations are made by Muffat et al. [71] , who demonstrate that overproduction of the human apoD are also associated with significantly reduced lipid peroxidation products, protecting against oxidative stress and extending lifespan by about 40% in fruit flies. Together these data demonstrate an evolutionally conserved safeguarding mechanism by which apoD acts to protect against lipid peroxidation and oxidative stress.