STEROL SIDE-CHAIN LENGTH AND STRUCTURE AFFECT THE CLEARANCE OF CHYLOMICRON-LIKE LIPID EMULSIONS IN RATS AND MICE

In previous work we found that sterols such as cholesterol were essent ial for physiological plasma clearance of lipid emulsions mimicking th e structure of mammalian triglyceride-rich lipoproteins. In the presen t study we compared the clearances of emulsions prepared with sterols of varying alkyl chain length (straight chains, n-C3 to n-C7, or branc hed chains, i-C5 to i-C10) at the C-17 position. Our studies show that the length of the alkyl chain at the C-17 position of sterols markedl y affects the removal of remnant particles from the plasma of rats tra ced by emulsion cholesteryl oleate label. An alkyl chain of 7 carbons or more was needed for normal remnant clearance. Straight and branched chains of similar length were cleared similarly, showing that the pre sence of a branch at the end of the alkyl chain had no effect on remna nt clearance. For side chains of 7 carbons or less, substitution of st erols with an unsaturation in the alkyl chain close to the terminal ca rbon markedly decreased the clearance of remnants. Triolein label was used to estimate lipolysis of the injected emulsions. Lipolysis was li ttle affected by the structure of the sterol side chain, except that l ipolysis was markedly higher with emulsions containing sterols with an alkyl chain having 4 carbon atoms (n-C4) or with an unsaturation in t he 4 carbon alkyl chain. We conclude that the length of the alkyl side chain is an important element in the essentiality of cholesterol as a regulator of metabolism of lipid emulsion models of triglyceride-rich lipoproteins.