Regulation of indices of cholesterol synthesis in human mononuclear leukocytes by dietary cholesterol and fat saturation.
The responses of 2 indices of cholesterol synthesis, 3-hydroxy-3-methylglutaryl-CoA reductase activity and incorporation of [14C]acetate into sterols, in mononuclear leukocytes freshly isolated from peripheral blood to variation in the ratio of saturated to unsaturated fat (S:U) and the amount of cholesterol absorbed from the diet were examined in 24 free-living men. Increasing S:U was associated with increasing plasma cholesterol level (r = 0.27, P = 0.03) and increasing reductase activity in leukocytes (r = 0.60, p less than 0.001). This finding is consistent with the hypothesis that saturated fat decreases the flux of cholesterol from plasma into cells thereby releasing reductase from product feedback inhibition. Reductase activity, after controlling for the effect of S:U, was negatively correlated with absorbed cholesterol from sources other than eggs (r = 0.42, P = 0.02). Surprisingly, change in reductase activity was positively correlated with change in absorbed cholesterol upon eating eggs (r = 0.49, P = 0.008). Sterol labeling was negatively correlated with absorbed cholesterol from all sources including eggs (r = -0.64, P less than 0.001) and was uncorrelated with S:U. Reductase activity and sterol labeling responded in parallel to cholesterol in foods other than eggs but not to egg feeding nor to S:U, thus it is unclear which test best reflects endogenous sterol synthesis in these cells.
Department of Medicine, Cornell University Medical College, New York, NY.
N L
NL
Young
D J
DJ
McNamara
G
G
Willems-de Harven
D002784:Cholesterol / Q000097:blood*; D002791:Cholesterol, Dietary / Q000008:administration & dosage*; D004041:Dietary Fats / Q000008:administration & dosage*; D004042:Dietary Fats, Unsaturated / Q000008:administration & dosage; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D013261:Sterols / Q000097:blood
D002791:Cholesterol, Dietary; D004041:Dietary Fats; D004042:Dietary Fats, Unsaturated; D008055:Lipids; D013261:Sterols; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases