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

Abstract

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-macrophages accumulated significantly more triglycerides than control cells: 987.6 +/- 26.8 vs. 779.3 +/- 24.1 micrograms/mg protein (P less than 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 micrograms/ml); it induced a significant increase of cellular cholesteryl ester content (21.9 +/- 1.1 vs. 11.7 +/- 1.7 micrograms/mg protein; P less than 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 less than 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.