The specificity of bile salts in the intestinal absorption of micellar cholesterol in the rat.

1. Two aspects of cholesterol absorption; (a) the importance of solubilization and (b) the effects of different bile salts on the mucosal metabolism and lymphatic output of cholesterol, have been investigated using two different in vivo techniques. 2. Bile diverted lymph fistula rats were infused intraduodenally at a steady rate with a constant lipid mixture containing labelled cholesterol, labelled oleic acid and mono-olein. The lipids were completely solubilized in either bile salts or a non-toxic non-ionic detergent, Pluronic F68. Labelled fatty acid was efficiently absorbed from either micellar infusate but virtually no labelled cholesterol appeared in the lymph in the absence of bile salts. 3. Short-term perfusions of the intestine of anaesthetized rats with the same micellar perfusates as above showed approximately 20% of the labelled cholesterol in the mucosa after 30 min perfusion with the bile salt micellar solutions. When the non-ionic micelles were used virtually no isotopic cholesterol left the lumen. 4. Mucosal uptake of labelled cholesterol was linearly dependent on the concentration of solubilized cholesterol in the perfusate and was not dependent on the bile salt concentration. 5. After 30 min the total amount of perfused isotopic cholesterol was recovered from either the lumen or the mucosa, but some fatty acid appeared to have been transported away from the mucosa by this time. 6. The initial rate of mucosal uptake of labelled cholesterol was similar from micellar perfusates using either taurocholate, taurodeoxycholate or taurofusidate. In contrast, after 8 h of infusion, lymphatic output of labelled cholesterol was markedly greater with taurocholate. 7. The increased lymph output with taurocholate was associated with an increase in the esterified fraction of both labelled and unlabelled cholesterol. Fatty acid was absorbed and esterified equally from all three types of perfusate. 8. These results suggested that for the first step in cholesterol absorption, viz. uptake from the lumen, solubilization by a planar detergent was essential. After uptake, the more rapid transfer of cholesterol to lymph in the presence of trihydroxybile acids appeared to be related to a more efficient esterification of cholesterol, but not to a more efficient resynthesis of triglyceride, the other major component of lymph chylomicrons.