AJP - Endocrinology and Metabolism, Vol 257, Issue 2 E290-E295, Copyright © 1989 by American Physiological Society
1,25-Dihydroxyvitamin D3-induced alterations of lipid metabolism in human monocyte-macrophages
J. B. Roullet, M. Haluska, O. Morchoisne and D. A. McCarron
Oregon Health Sciences University, Portland 97201.
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.
