1,25-Dihydroxyvitamin D₃-induced alterations of lipid metabolism in human monocyte-macrophages

An in vivo atherogenic role of dietary vitamin D has been postulated. To address this hypothesis we sought to determine the in vitro effects of its active circulating metabolite, 1,25-dihydroxyvitamin D₃ [1,25(OH)₂D₃] on lipid metabolism in human monocyte-derived macrophages. When cultured 6 days in the presence of 10^-8 M 1,25(OH)₂D₃ monocyte-macrophage accumulated significantly more triglycerides than control cells: 987.6 ± 26.8 vs. 779.3 ± 24.1 μg/mg protein (P < 0.001). Triglyceride accumulation was associated with a hormone-induced stimulation of triglyceride synthesis as determined by [³H]oleate incorporation into cellular triglycerides. The effect of the hormone was significant after 24 h and dose dependent [10^-11 to 10^-8 M 1,25(OH)₂D₃]. It was specific since 10^-7 M 25-hydroxyvitamin D₃ and 24,25-dihydroxyvitamin D₃ did not stimulate triglyceride synthesis, and its magnitude decreased from 1 to 9 days of culture. 1,25(OH)₂D₃ (10^-8 M) modified the cholesteryl ester metabolism of monocyte-macrophages only in the presence of acetylated low-density lipoproteins (50 μg/ml); it induced a significant increase of cellular cholesteryl ester content (21.9 ± 1.1 vs. 11.7 ± 1.7 μg/mg protein; P < 0.001) and of esterification rate of cholesterol measured by [³H]oleate incorporation into cellular cholesteryl esters (17.2 ± 0.9 vs. 6.5 ± 0.3 nmol·mg protein^-1·24 h^-1; P < 0.001) by comparison with control cells. These results show that 1,25(OH)₂D₃ alters in vitro lipid metabolism in the human monocyte-macrophage and suggest a new in vivo role for the hormone.