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-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.
Oregon Health Sciences University, Portland 97201.
J B
JB
Roullet
M
M
Haluska
O
O
Morchoisne
D A
DA
McCarron
D002117:Calcitriol / Q000494:pharmacology*; D002478:Cells, Cultured; D002784:Cholesterol / Q000097:blood; D002788:Cholesterol Esters / Q000097:blood; D006801:Humans; D007700:Kinetics; D008055:Lipids / Q000097:blood*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D019301:Oleic Acid; D009829:Oleic Acids / Q000097:blood; D012016:Reference Values; D014280:Triglycerides / Q000096:biosynthesis / Q000097:blood
D002788:Cholesterol Esters; D008055:Lipids; D009829:Oleic Acids; D014280:Triglycerides; D019301:Oleic Acid; D002784:Cholesterol; D002117:Calcitriol