25‐Hydroxycholesterol 3‐sulfate regulates lipid metabolism via SREBP‐1 in human macrophages

Abstract

Macrophages are the most prominent cell type in atherosclerotic lesions. The earliest atherosclerotic lesions are characterized by the accumulation of foam cells in the arterial wall. The foam cells develop following the accumulation of lipids in macrophages. To reduce the accumulation or increase the elimination of lipids in macrophages is central to prevent the development of atherosclerotic foam cells. We have found that 25‐hydroxychosterol 3‐sulfate (25HC3S) plays an important role in lipid metabolism in hepatocytes. In the present study, we further examined the role of this oxysterol in lipid metabolism in macrophages. The results indicate that treatment of human leukemia cell line derived macrophages with 25HC3S decreased expression of sterol regulatory element binding protein and of its downstream targeting genes encoding key enzymes, fatty acid synthase (FAS), acetyl CoA carboxylase (ACC‐1), and HMG reductase, which are involved in fatty acid and cholesterol biosynthesis; Oil‐Red O staining and MTT cell proliferation assay showed that 25HC3S decreased intracellular lipid accumulation and increased the cell viability in the oxidized low density lipoprotein‐treated cells, which were opposite to the effect of 25‐hydroxycholesterol. These studies suggest that 25HC3S is a potent regulator of lipid metabolism in macrophages and may be useful for prevention and therapy of atherosclerosis.