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.
|Original language||English (US)|
|Journal||American Journal of Physiology - Endocrinology and Metabolism|
|State||Published - 1989|
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Physiology (medical)