Adipocyte-derived plasma protein, adiponectin, suppresses lipid accumulation and class A scavenger receptor expression in human monocyte-derived macrophages

Background-Excessive lipid accumulation in macrophages plays an important r ole in the development of atherosclerosis. Recently, we discovered an adipo cyte-specific plasma protein, adiponectin, that is decreased in patients wi th coronary artery disease. We previously demonstrated that adiponectin act s as a modulator for proinflammatory stimuli and inhibits monocyte adhesion to endothelial cells. The present study investigated the effects of adipon ectin on lipid accumulation in human monocyte-derived macrophages. Methods and Results-Human monocytes were differentiated into macrophages by incubation in human type AB serum for 7 days, and the effects of adiponect in were investigated at different rime intervals. Treatment with physiologi cal concentrations of adiponectin reduced intracellular cholesteryl ester c ontent, as determined using the enzymatic. fluorometric method. The adipone ctin-treated macrophages contained fewer lipid droplets stained by oil red O. Adiponectin suppressed the expression of the class A macrophage scavenge r receptor (MSR) at both mRNA and protein levels by Northern acid immunoblo t analyses, respectively, without affecting the expression of CD36, which w as quantified by flow cytometry. Adiponectin reduced the class A MSR promot er activity, as measured by luciferase reporter assay. Adiponectin treatmen t dose-dependently decreased class A MSR ligand binding and uptake activiti es. The mRNA level of lipoprotein lipase as a marker of macrophage differen tiation was decreased by adiponectin treatment, but that of apolipoprotein E was not altered. Adiponectin was detected around macrophages in the human injured aorta by immunohistochemistry. Conclusions-The adipocyte-derived plasma protein adiponectin suppressed mac rophage-to-foam cell transformation, suggesting that adiponectin may act as a modulator for macrophage-to-foam cell transformation.