A mutual inhibitory effect on absorption of sphingomyelin and cholesterol

Several studies have shown that there is a strong physical inter-action bet ween cholesterol and sphingomyelin (SM). The clinical factor is thought to be the high degree of saturation in the very long acyl chains of SM. In thi s study we examined the effects of SM on cholesterol absorption in the rat and compared them with those of phosphatidylcholine (PC) Cholesterol absorp tion was studied by use of the dual-isotope plasma ratio method. We also st udied the effect of sterols on the fecal excretion of undigested SM and its metabolites after a single oral meal of H-3-dihydrosphingosine-labeled SM. When cholesterol was given dissolved in soybean oil, without addition of S M or other phospholipids, absorption was 68 +/- 12% in the rat intestine. A s a general feature the absorption was less efficient from the cholesterol/ phospholipid dispersions. In dispersions with cholesterol and SM, the lowes t cholesterol absorption (9 +/- 2%) was seen with a cholesterol:SM molar ra tio of 1:1. With dispersions of cholesterol and different PC substrates the absorption of cholesterol was lower with saturated PC (16+/- 8%) than with soybean-PC (22 +/- 4%) or dioleoyl PC (23 +/- 8%). Uptake of SM in the rat intestine was reduced by sterols. For example, percentage recovery of H-3 radioactivity in fecal lipids was 38 +/- 8% when SM was given with choleste rol and 16 +/- 3% without any sterol. One third of the radioactivity in fec es was present ar ceramide. Sitostanol had rite same effect an uptake of SM as cholesterol. This study short's that when rats are fed mixtures of SM a nd cholesterol the intestinal uptake of hath lipids is decreased. By feedin g mixtures of SM and sterols the exposure of the colon to ceramide can he i ncreased. (C) Elsevier Science Inc. 2000. All rights reserved.