Intestinal absorption and lymphatic transport of cholesterol in the rat: influence of the fatty acid chain length of the carrier triglyceride

This paper deals with the effect of the fatty acid chain length of dietary triglyceride on the intestinal uptake and lymphatic transport of exogenous and endogenous cholesterol in the rat. This question seemed of interest as the chain length of the monoglyceride and fatty acids formed in the intestinal lumen from the triglyceride fed could be expected to affect the concentration of cholesterol in the micellar or isotropic phase of intestinal content. Feeding rats medium- or short-chain triglycerides (C(12) to C(2)) did not affect the lymphatic transport of endogenous cholesterol from the intestine compared to the fasting state. The extent of lymphatic transport of cholesterol added to these fats increased proportionally with chain length (C(6)-C(18)) of the component fatty acids. The uptake of exogenous cholesterol into the intestinal wall was similarly related to the chain length of the carrier triglyceride, with the exception of triacetin, which gave a much higher intestinal uptake than lymphatic transport. When cholesterol was fed in octadecane, negligible amounts only were transported to the thoracic duct lymph. This again indicates the importance of the polar split products of dietary fat for cholesterol absorption.     

Absorption and lymphatic transport of cholesterol and sitosterol in the rat

An attempt was made to determine the mechanism for the greater absorbability of cholesterol as compared to sitosterol. Sitosterol-22,23-(3)H in different combinations with cholesterol-4-(14)C, dissolved in 0.8 ml of triolein, was fed to rats with lymph fistulae. Feeding 1.5, 50, or 100 micro moles of sitosterol resulted in a transfer to the lymph in 24 hr of 3-6% of the sitosterol, largely independent of the dose fed. The total amount of sitosterol transferred to the lymph was therefore almost linearly related to the dose fed. 30% of a tracer dose of cholesterol-4-(14)C fed together with the sitosterol was transferred to the lymph in 24 hr. When a total of 50 micro moles of sterol, containing cholesterol-(14)C and sitosterol-(3)H in the proportions 1:3, 1:1, and 3:1, was similarly fed, we found that sitosterol had no significant effect on the lymphatic transport of the simultaneously fed cholesterol. The ratio of (3)H to (14)C in the lymph was between 0.1 and 0.2 (the ratio in each fed mixture being taken as 1.0). The ratio was constant during the absorption period and independent of the ratio of sterols in the fed sterol mixture. Thus the same percentage of each sterol was always absorbed, and the sterols exerted no mutual interference in each others' absorption. We conclude that the mechanism for specificity in sterol absorption must be located early in the transport of the sterols within the intestinal mucosa cell.     

Effects of tetrahydrolipstatin, a lipase inhibitor, on absorption of fat from the intestine of the rat

Tetrahydrolipstatin (THL) derived by hydrogenation from lipstatin, a lipase inhibitor produced by Streptomyces toxytricini, has been shown to inhibit in vitro the activity of all three lipases secreted to the gastro-intestinal tract; gastric lipase, pancreatic lipase and carboxylester lipase (cholesterol ester hydrolase). The effects of THL on intestinal absorption of fat (transport to the thoracic duct chyle) has now been investigated after intraduodenal infusion in a rat model. Absorption of label from oleic acid when administered with monoolein in micellar bile salt solution was not affected by THL in concentrations up to 10(-4) M calculated on the volume of the aqueous phase. Absorption of free cholesterol in micellar bile salt solution of the lipolytic products of triolein; oleic acid and monoolein, is not significantly affected at a concentration of THL of 10(-4) M. Absorption of cholesterol from cholesteryl oleate under the same conditions is almost completely inhibited. The results indicate that absorption of free cholesterol is not dependent on the activity of pancreatic cholesterol ester hydrolase. The absorption of emulsified triolein was not significantly affected by 10(-5) M THL but decreased to around 30% of the controls by a concentration 10-times higher. There was no significant decrease of cholesterol absorption when administered in emulsified triolein while absorption of cholesteryl oleate was reduced at both concentrations of THL and almost completely at 10(-4) M. Radioactivity from [2-14C]THL when administered emulsified in triolein was recovered in urine, bile and thoracic duct lymph to 10-14, 8-13 and 1-3%, respectively, largely independent on dose administered. Label from [1"-14C] THL was recovered in the same amounts in lymph but much less in bile and urine indicating that the amino acid moiety has been split off early in the absorption process.     

Transmucosal triglyceride transport rates in proximal and distal rat intestine in vivo.

Transmucosal transport rates for triolein in proximal and distal intestine were compared in unanesthetized rats. Emulsified [1-14-C] triolein together with bile and pancreatic juice from donor rats was infused for 6 hr into either the duodenum or the midpoint of the small intestine at such a rate that absorption was essentially complete in both regions of the intestine. Lymph was collected from the thoracic duct during triolein infusion and for an additional 6-hr period. The decrease in the rate of lymphatic output of labeled fat was found to follow a simple exponential function in all animals. This rate of decrease (decay rate) was used to calculate the half-times of lipid turnover through the intestinal wall and the fractional output rates. Distal intestine transported lipid 40% more slowly than proximal intestine, and the difference was associated with a greater accumulation of triglyceride in the distal intestinal wall. Chylomicron synthesis and/or release is the rate-limiting step for distal lymphatic fat transport in vivo, whereas fat uptake from the lumen is rate limiting for proximal intestine.     

Cholesterol absorption and transport in thoracic duct lymph lipoproteins of nonhuman primates. Effect of dietary cholesterol level

The effect of dietary cholesterol level on cholesterol absorption and its subsequent transport in thoracic duct lymph lipoproteins was studied in two species of nonhuman primates, namely the African green monkey (Cercopithecus aethiops) and the cynomolgus macaque (Macaca fascicularis). Each animal served as its own control because each received sequential, intraduodenal infusions of two fat-rich liquid diets that differed only in the amounts of cholesterol. The percentage of dietary cholesterol absorbed was calculated by dividing the rate of appearance of exogenous cholesterol radioactivity in lymph by the rate of infusion of dietary cholesterol radioactivity at a time when lymph cholesterol specific activity was constant relative to that of diet. The percentage of dietary cholesterol absorbed was similar during both diet infusions in African green monkeys but was significantly decreased during the high cholesterol diet infusion in cynomolgus macaques. Rates of appearance of lymph total cholesterol mass were significantly increased during infusion of high cholesterol diets due to a statistically significant increase in cholesteryl ester transport rates. This increase was due in large part to the preferential esterification of exogenous cholesterol that was incorporated into lymph chylomicrons and VLDL. The rate of appearance in lymph of exogenous cholesterol significantly increased during the high cholesterol diet infusion while that of endogenous cholesterol decreased. This decrease or compensation in endogenous cholesterol transport occurred during absorption of increased levels of dietary cholesterol and apparently was due to an approximate 50% decrease in the absorption of lumenal cholesterol. Our data demonstrated that there was not a simple one-to-one relationship between the amount of isotopic dietary cholesterol absorbed from the intestinal lumen and the mass of cholesterol moved into lymph via the intestine. Rather, the amount of sterol transported into the body depends on the degree of the decrease in endogenous cholesterol transport and probably on the efficiency of cholesterol esterification during absorption.     

Lymphatic absorption of fatty acids and cholesterol in the neonatal rat

High-fat diets are essential in suckling animals to ensure adequate calories for postnatal growth, but their lymphatic transport of dietary lipids has not been characterized. We established a lymph fistula model in suckling rats to quantify intestinal uptake and lymphatic transport of dietary lipids and analyzed lipoprotein fractions. Suckling 19-day-old Sprague-Dawley rats had their mesenteric lymph ducts cannulated and gastroduodenal tubes inserted. After overnight recovery, [(3)H]triolein and [(14)C]cholesterol were infused for 6 h. Of the total dose, only 38% of triolein and 24% of cholesterol were transported in the lymph of suckling rats. Analyses of residual luminal contents and intestinal mucosal homogenate showed neither reduced absorption nor delayed mucosal processing of ingested lipids to be the cause. Thin-layer chromatographic analysis of radioactive mucosal lipids, however, showed a predominance of free fatty acids (60%) and free cholesterol (67%), implying impaired esterification capacity in these animals. We speculate that this reduced esterification allows for portal transport or direct enterocyte metabolism of dietary lipids.     

Effect of copper deficiency on the lymphatic absorption of cholesterol, plasma chylomicron clearance, and postheparin lipase activities

The lymphatic absorption of cholesterol and plasma clearance of chylomicrons were investigated in Cu-deficient rats (CuD) fed 0.5 mg Cu/kg diet, as compared with Cu-adequate control rats (CuA) fed 7.5 mg/kg diet. Cholesterol absorption was measured by the 14C-radioactivity appearing in the mesenteric lymph at hourly intervals for 8 hr after an intraduodenal dose of [14C]cholesterol. The plasma clearance of chylomicrons was measured at 3, 6, and 10 min after an intravenous dose of chylomicrons labeled in vivo with [3H]retinyl ester. Cumulative [14C]cholesterol absorption and total lymphatic output of cholesterol were significantly decreased in CuD at 4 hr and thereafter, with no change in percentage distribution of free and esterified cholesterol. Over an 8-hr period, 7.3% of the dose was absorbed by CuD and 9.2% by CuA. When [3H]chylomicrons, obtained from a CuD or CuA donor rat, were injected into CuD and CuA recipient rats, the label was cleared faster in CuD during the first 3 min. At 6 and 10 min, however, no significant difference in percentage clearance of the dose was observed between the groups. The half-life (t1/2) of [3H]chylomicrons and the total 3H-radioactivity taken up by the liver during the entire 10-min period did not differ between the groups, regardless of the source of chylomicrons. The activities of both endothelial lipoprotein lipase (LPL) and hepatic lipase (HL) in postheparin plasma were markedly lower in CuD. As expressed in micromoles fatty acid released/hr/ml plasma, the activities of LPL in CuD and CuA were 32.6 +/- 1.9 and 45.6 +/- 1.3, respectively. A similar magnitude of difference was also observed in HL activity. The data provide evidence that copper deficiency impairs the intestinal transport of cholesterol and the peripheral lipolysis of chylomicrons. The data, however, strongly suggest that the hepatic uptake of chylomicron remnants via the apo-E-dependent mechanism may not be impaired in Cu deficiency.     

Inhibitory action of gemfibrozil on cholesterol absorption in rat intestine

This study was designed to determine whether gemfibrozil inhibits intestinal lipid absorption. Male Sprague-Dawley rats received an oral dose of 30 mg gemfibrozil/kg body weight for 14 days. Mesenteric lymph cannulation was performed, and a lipid infusion containing 40 micromol/h (35.4 mg/h) of radiolabeled triolein and 2.74 micromol/h (1.06 mg/h) of radiolabeled cholesterol with the addition of 1 mg/h of gemfibrozil was infused intraduodenally at a rate of 3 ml/h for 8 h. The lymph was collected, and the radioactivity levels of the lumen and gut mucosa were measured after the infusion. Lymph cholesterol transport was depressed in gemfibrozil-treated rats, in terms of mass measurements as well as radioactivity in a lesser degree. More radioactive cholesterol remained in the proximal portion of the intestinal lumen and mucosa in the treated rats than in the control rats. More radioactive triglycerides also remained in the proximal intestinal lumen of treated rats, although no difference in lymphatic triglyceride transport was observed between the groups. A significant portion of the radioactive cholesterol remained in the lumen in the gemfibrozil-treated rats. Gemfibrozil increased biliary cholesterol excretion. Thus, this study shows that gemfibrozil inhibits cholesterol absorption in rat intestine.     

Effect of rutin on the cholesterol content of the lymph, blood and tissues of the dog

It has been discovered in experiments on mongrel dogs anesthetized with morphine and hexenal that intravenous injection of rutin (3 mg/kg bw) reduced the concentration of total, esterified and free cholesterol in blood serum, with the exception of free cholesterol level in arterial blood, which increased. Under the same conditions, the concentration of free and esterified cholesterol in thoracic duct lymph ascended. In the popliteal lymph node, gastrocnemius muscle and liver, the content of total cholesterol appreciably dropped as compared to control. Rutin has been found to accelerate the lymph flow and to raise cholesterol resorption from the interstitial space. It is inferred that lymph plays an important part in cholesterol transport in the body.     

Serum and lymph lipids in rabbits with carbon tetrachloride-induced cirrhosis of the liver

Lymph flow and the composition of lymph lipids from the hepatic and thoracic ducts of rabbits with cirrhosis of the liver (induced by 46-51 intramuscular injections of a mixture of carbon tetrachloride and olive oil at 4-day intervals) have been compared with those of control animals injected with olive oil only. In cirrhotic animals, the concentration of lymph lipids was not greatly altered, but lymph flow, and consequently the hourly transport of lipids by lymph were greatly increased; the increase in transport of cholesteryl esters, free cholesterol, and phospholipids by way of the thoracic and hepatic duct lymph was particularly striking. The concentration of these lipid fractions in serum from the cirrhotic rabbits was also increased. The differences normally observed between lipid fatty acid compositions of serum and lymph disappeared in cirrhotic animals; this is interpreted as due to increased hepatic permeability to lipoproteins.     

Polychlorinated biphenyl uptake and transport by lymph and plasma components

The uptake and vascular transport of ingested Aroclor 1242, an isomeric mixture of polychlorinated biphenyls (PCB), was investigated in experimental animals. High concentrations of ingested PCB were found in the chylomicron fraction of thoracic duct lymph. When the lymph flow was exteriorized PCB were not subsequently found in the vascular circulation. When lymph was not exteriorized plasma PCB concentrations reached maximal levels 6 hr after ingestion. Less than 1% of total plasma PCB was detected in cellular fractions of blood over a 10-hr period following ingestion. Chylomicrons contained 31% of total plasma PCB 30 min after ingestion, decreasing to less than 6% at 4 hr. A maximum of 10% of plasma PCB at 1 hr, and less than 5% at 6 hr, after ingestion was associated with very low density lipoproteins (VLDL) or low density lipoproteins (LDL). Although PCB enter the vascular circulation with the chylomicron fractions of lymph, delipoproteinated plasma contained 52% of the total PCB in blood collected 30 min after ingestion. This level increased to 78% after 2 hr, and remained constant at about 80% for an additional 8-hr period. High performance liquid chromatographic (HPLC) examinations of delipoproteinated plasma from blood taken 6 hr after PCB ingestion showed elution of greater than 95% of plasma PCB to coincide with the albumin peak. Electrophoretic examinations of delipoproteinated plasma showed the association of PCB with albumin to be noncovalent. The results suggest that apolar PCB are absorbed into intestinal epithelial cells from which they are secreted into the lymphatic drainage sequestered within the apolar core of chylomicrons, that these PCB transit the thoracic duct and enter the vascular circulation within chylomicrons and are metabolized or otherwise released from chylomicrons during hepatic chylomicron clearance, and that resulting PCB or PCB derivatives circulate in association with plasma albumins.     

Cholesterol absorption and turnover in hypercholesterolemic dogs

Cholesterol absorption was measured in chronically hypercholesterolemic dogs by four methods: the fecal recovery method of Borgstr?m (1969, J. Lipid Res. 10: 331-337), the dual isotope method of Zilversmit and Hughes (1974, J. Lipid Res. 15: 465-473), the recovery of cholesterol in thoracic duct lymph collected continuously for 16 hr after a meal, and the recovery of isotopic cholesterol from the liver and plasma 24 hr after the animals consumed an isotope-containing meal. The four methods showed excellent agreement and indicated that dogs fed a cholesterol-rich synthetic diet absorb 5.2 +/- 0.5 g (mean +/- SD) of cholesterol per day and that cholesterol absorption is reasonably constant from week to week in these animals. Separate estimates of cholesterol excretion indicated that these dogs excreted 4.7 +/- 0.5 g of cholesterol per day, and thus were at or near the steady-state with regard to cholesterol input-output. These data, taken together with a previous report (1981, J. Lipid Res. 22: 598-609), indicate that the canine liver can clear up to 300 mg of chylomicron cholesterol/hr, and support the concept that chylomicron remnants do not contribute significantly to the hypercholesterolemia in these animals.     

THE TEMPO OF LYMPHOCYTE RECIRCULATION FROM BLOOD TO LYMPH IN THE RAT

Radioactively labelled thoracic duct lymphocytes were obtained either by incubation in vitro with ³H-uridine or ¹⁴C-uridine or by giving potential donors repeated injections of ³H-thymidine finishing 17 days before thoracic duct cannulation. These labelled TDL were injected i.v. into syngeneic recipients which had been subjected to splenectomy and thoracic duct cannulation on the previous day. The tempo of lymphocyte recirculation from blood to lymph was reflected by the time at which radioactivity was recovered in the thoracic duct lymphocyte output of the recipient. This was measured by scintillation counting of 2-hourly fractional collections for 36 hr after the injection. Two lines of evidence showed that the majority of small lymphocytes which label intensely with radioactive uridine in vitro were uniform in their 'migration potential'with a modal blood to lymph transit time of 14–18 hr. By contrast the cells which were labelled in vivo with ³H-thymidine included a slower population with a modal transit time of 24–28 hr. These conclusions can be more fully interpreted in the light of recent evidence on thymic-independent ('B') lymphocytes.     

Quantitative aspects of the intestinal absorption and metabolism of cholesterol and beta-sitosterol in the rat

The quantitative aspects of intestinal absorption and metabolism of cholesterol and -sitosterol have been studied in the rat after a single feeding of radioactive sterols. When increasing amounts of cholesterol were fed in a constant amount of triolein, the percentage absorbed decreased only gradually and the total amounts absorbed increased to a maximum. Solubility in the fat component fed is one limiting factor in the absorption of cholesterol. At the lowest dose fed, only about 50% of dietary cholesterol was absorbed even though increasing the amount fed led to a 10- to 15-fold increase in total absorption. Sitosterol, when fed in triolein, was absorbed in amounts only one-tenth of the corresponding dose of cholesterol. Intestinal transit studies indicate that the distinction between sitosterol and cholesterol, when fed together, took place during the process of uptake into the intestinal mucosa. Once taken up by the intestinal mucosal cells, cholesterol and sitosterol did not differ in their subsequent rate of transit out of the mucosal cell. Feeding sitosterol with cholesterol seems to have the same effect on cholesterol absorption as feeding the same additional dose of cholesterol, the difference being that sitosterol is taken up by the intestinal wall in amounts only one-tenth to one-fifth of that of cholesterol. The rapid and complete absorption of the triglyceride fat and the subsequent transit of the intestinal content to the large intestine are most probably important factors in the determination of the extent of absorption of nonglyceride fat. The mechanism behind the difference in extent of absorption of the closely related sterols is not explained.     

Origin of cholesterol transported in intestinal lymph: studies in patients with filarial chyluria

In subjects fed a cholesterol-free diet there are three possible sources of intestinal lymph cholesterol: a) mucosal synthesis; b) absorption of endogenous (biliary) cholesterol; and c) transudation of plasma lipoproteins into the lacteals of the intestinal wall. To test these possibilities, the extent of transudation was measured by means of [3H]beta-sitosterol administered intravenously as a marker. Absorption of biliary cholesterol was reduced by oral administration of beta-sitosterol (9 g/day), and mucosal synthesis of cholesterol was evaluated by comparisons of plasma/lymph [14C]cholesterol specific activity ratios after intravenous administration of a single dose of labeled cholesterol. Studies were carried out on six patients with filarial chyluria. In five patients fed a cholesterol-free diet the results indicated that lymph cholesterol was largely derived by transudation of plasma lipoproteins into the lacteals from the intestinal blood supply, without contribution from de novo mucosal synthesis or from absorption of endogenous cholesterol. The intestinal lymph of one patient fed cholesterol (2 g/day) contained cholesterol originating mostly from plasma transudation and from dietary absorption, with little contribution from absorbed endogenous cholesterol. In all experiments the larger part of the cholesterol transported away from the intestine in the lymph was carried in chylomicrons, even though it had its origin in plasma lipoproteins.     

Nanoparticle Transport from Mouse Vagina to Adjacent Lymph Nodes

To test the feasibility of localized intravaginal therapy directed to neighboring lymph nodes, the transport of quantum dots across the vaginal wall was investigated. Quantum dots instilled into the mouse vagina were transported across the vaginal mucosa into draining lymph nodes, but not into distant nodes. Most of the particles were transported to the lumbar nodes; far fewer were transported to the inguinal nodes. A low level of transport was evident at 4 hr after intravaginal instillation, and transport peaked at about 36 hr after instillation. Transport was greatly enhanced by prior vaginal instillation of Nonoxynol-9. Hundreds of micrograms of nanoparticles/kg tissue (ppb) were found in the lumbar lymph nodes at 36 hr post-instillation. Our results imply that targeted transport of microbicides or immunogens from the vagina to local lymph organs is feasible. They also offer an in vivo model for assessing the toxicity of compounds intended for intravaginal use.     

Role of the lymphatic system in the transport of biologically active substances in shock of various etiologies

The content of histamine, serotonin, adrenaline and noradrenaline in the thoracic and lymphatic duct lymph and blood as well as absolute quantity of lymph transported biogenic amines and mediators into the general circulation were studied on 68 dogs during anaphylactic and endotoxin shock (ASh and ESh, respectively). Both ASh and ESh were accompanied by considerable changes in the hemodynamics, lymph circulation, content of biologically active substances in lymph and blood and in their lymph transport to the blood stream. The most profound and early changes in the content of biologically active substances during ASh and ESh were found in the lymph, which shows an important role of the lymphatic system in their resorption and transport from organs and tissues into the general circulation.     

The migration of lymphocytes across specialized vascular endothelium. IV. Prednisolone acts at several points on the recirculation pathways of lymphocytes

Radioactively labelled thoracic duct lymphocytes from syngeneic rat donors were injected iv into recipients which had been given a continuous iv infusion of prednisolone at 1 mg/hr for 15–18 hr previously. The tissue distribution and recirculation into lymph of the labelled lymphocytes were compared quantitatively in the prednisolone-treated and control recipients by scintillation counting and autoradiography. The most prominent effect of prednisolone was to retard recirculating lymphocytes within the tissues to which they are normally distributed by the blood, namely the bone marrow, the spleen, and the lymph nodes. Although lymphocyte traffic was almost completely frozen by prednisolone, recirculating lymphocytes were not killed. A second effect of prednisolone was to impair the influx of lymphocytes from the blood into lymph nodes. Different groups of lymph nodes varied in the extent to which prednisolone inhibited the entry of lymphocytes, and previous antigenic stimulation completely exempted lymph nodes from this inhibition. Lymphocytes took a longer time to cross the walls of high endothelial venules in the lymph nodes of prednisolone-treated rats. A third effect of prednisolone was to increase the rate at which lymphocytes entered the bone marrow from the blood by crossing sinusoidal endothelium.     

Factors regulating the formation of chylomicrons and very-low-density lipoproteins by the rat small intestine

The aim of this study was to investigate how the relationship between chylomicron and very-low-density lipoprotein (VLDL) transport of fatty acid into lymph was affected by the total amount of lipid transported via the intestinal lymphatics in the rat. Two different experimental conditions were employed. First, intestinal lymph fistula rats were infused with four different levels of [3H]oleic acid (15, 30, 60 and 120 mumol per h) at a constant rate for 8 h. Lymphatic transport of [3H]oleic acid via chylomicrons and VLDLs was measured in lymph collected during the seventh h. Within the dose range studied chylomicron increased exponentially, while the output in VLDL reached a plateau at a total lymph [3H]oleic acid output of approx. 60 mumol/h. A linear regression analysis of the ln(chylomicron/VLDL) versus the total output in lymph yielded a coefficient of correlation of 0.95. Second, we utilized the fact that intraduodenal infusion of the nonionic detergent Pluronic L-81 (L-81) inhibits chylomicron transport and that this inhibition is reversed by the cessation of L-81 infusion (unblocking). A linear regression analysis of the ln(chylomicron/VLDL) versus total lymph [3H]oleic acid output during the first 4 h of unblocking gave a coefficient of correlation of 0.79. Statistical analysis of the regression equations from the two experiments showed that for the same lymphatic [3H]oleic acid output, the chylomicron/VLDL ratio was significantly lower in the L-81 experiment, indicating that the relative rates of formation of chylomicron to VLDL were different under these two experimental conditions. However, the principal pattern was the same, i.e., chylomicron production increased, while VLDL production became saturated when the amount of oleic acid transported to the lymph was increased.     

Inhibition of lymphatic absorption of cholesterol by cholestane-3 beta, 5 alpha, 6 beta-triol

The effect of cholestane-3,5alpha,6-triol (CT) on the intestinal absorption of cholesterol and oleic acid, as well as the absorption of labeled CT, was studied in lymph ductcannulated rats. Intragastric administration of 50 mg of CT in an emulsion with cholesterol-7alpha-(3)H and oleic acid-1-(14)C resulted in 50% inhibition of sterol transfer into lymph but only 8% depression of fatty acid absorption over an 8 hr period. The absorption of labeled CT into lymph was only 2-3% compared with 50% absorption of cholesterol when each was fed alone. 10% of the fed CT was recovered in the intestinal mucosa, and of this, one-half was associated with the brush border fraction. In rats fed CT 6 days prior to cholesterol and fatty acid administration, there was no effect on fatty acid absorption, while cholesterol absorption was reduced by almost 30%. When the intestinal mucosa from these animals were investigated by electron microscopy, it appeared that CT feeding resulted in numerous enlarged mitochondria and a marked increase in length of the microvilli. If animals were allowed to recover for 6 days from the CT prefeeding regime, the intestinal mucosa appeared normal, and the absorption of cholesterol approached that in controls. A possible mechanism for CT inhibition of cholesterol absorption was shown to be competition for the enzyme cholesterol esterase which esterifies cholesterol prior to entrance into the lymphatic system. CT itself is poorly esterified and poorly absorbed, but it is effective in inhibiting esterification of cholesterol in vitro.