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.     

Inhibition of cholesterol absorption in rats by plant sterols

The extent and site(s) of inhibition of cholesterol absorption by plant sterols, sitosterol and fucosterol, were studied in rats. The intragastric administration of a single emulsified lipid meal containing 25 mg [3H]cholesterol and 25 mg of either sitosterol or fucosterol inhibited the lymphatic absorption of cholesterol by 57% and 41%, respectively, in 24 hr. Less than 2% of each plant sterol was absorbed in the 24-hr period. In contrast, neither plant sterol (50 microM) inhibited cholesterol absorption when co-administered with equimolar amounts of cholesterol in phospholipid-bile salt micelles nor was either absorbed from the micellar solution. A series of in vitro studies was conducted to identify the site(s) of plant sterol inhibition of cholesterol absorption and to account for the difference in inhibitory effectiveness of sitosterol and fucosterol. A comparison of the micellar solubility of each sterol alone and in equimolar binary mixtures (to 2.0 mM) revealed that the solubility of individual sterols decreased in the following order: cholesterol, fucosterol, sitosterol, and that in binary mixtures cholesterol solubility was decreased by sitosterol and, to a lesser extent, by fucosterol relative to its solubility alone. A comparison between micellar-solubilized cholesterol and either sitosterol or fucosterol for binding to isolated brush border membranes, intestinal mucin, or for esterification by either cholesterol esterase or acyl coenzyme A:cholesterol acyltransferase revealed moderate to no competition. The data suggest that plant sterols displace cholesterol from bile salt (taurocholate) micelles and that sitosterol is more effective than fucosterol in this capacity.     

Comparison of the intestinal uptake of cholesterol,plant sterols,and stanols in mice

The recent identification of the aberrant transport proteins ABCG5 and ABCG8 resulting in sitosterolemia suggests that intestinal uptake of cholesterol is an unselective process, and that discrimination between cholesterol and plant sterols takes place at the level of sterol efflux from the enterocyte. Although plant sterols are structurally very similar to cholesterol, differing only in their side chain length, they are absorbed from the intestine to a markedly lower extent. In order to further evaluate the process of discrimination, three different sterols (cholesterol, campesterol, sitosterol) and their corresponding 5 alpha-stanols (cholestanol, campestanol, sitostanol) were compared concerning their concentration in the proximal small intestine, in serum, and in bile after a single oral dose of deuterated compounds. The data obtained support the hypothesis that i) the uptake of sterols and stanols is an extremely rapid process, ii) discrimination probably takes place on the level of reverse transport back into the gut lumen, iii) plant stanols are taken up, but not absorbed to a measurable extent, and iv) the process of discrimination probably also exists at the level of biliary excretion. The range of structural alterations that decrease intestinal absorption and increase biliary excretion is: 1) campesterol, 2) cholestanol-sitosterol, and 3) campestanol-sitostanol.     

Effect of different dietary triglycerides on 7alpha-hydroxylation of cholesterol and other mixed-function oxidations

The effect of a diet containing triglycerides of different fatty acid composition on hepatic 7alpha-hydroxylation of cholesterol was studied. 7alpha-Hydroxylation of exogenous as well as endogenous cholesterol was significantly lower in the liver of rats fed trilinolein and triolein than in those fed tripalmitin and trierucin. The concentration of cytochrome P-450 in liver microsomes was significantly lower in the rats fed tripalmitin and trierucin than in those fed triolein and trilinolein. The inhibitory effect of triolein and trilinolein on 7alpha-hydroxylation of cholesterol and the stimulatory effect of these triglycerides on the concentration of cytochrome P-450 was not due to the small amounts of peroxides present in the unsaturated triglycerides. Thus addition of the antioxidant butylated hydroxyanisol did not change the general pattern with respect to 7alpha-hydroxylation and concentration of cytochrome P-450. However, a diet consisting of peroxidized linoleic acid further decreased 7alpha-hydroxylation of cholesterol. The difference between the effect obtained with triolein and trilinolein on the one hand and trierucin and tripalmitin on the other was observed also in experiments with lower concentrations of fat in the diet and in experiments with different lighting conditions and feeding patterns. The inverse relation between cytochrome P-450 and 7alpha-hydroxylation of cholesterol, as well as results obtained with substrates for mixed-function oxidation other than cholesterol suggest that most of the changes observed due to the different diets are specific for 7alpha-hydroxylation of cholesterol. The level of cholesterol 7alpha-hydroxylase activity was found to be better related to the degree of absorption of fat than to total amount of absorbed fat or degree of unsaturation of the fat. The results are discussed in relation to previous knowledge concerning mechanisms regulating biosynthesis of bile acid.     

Mechanisms for cholesterol homeostasis in rat jejunal mucosa: effects of cholesterol, sitosterol, and lovastatin

The effects of feeding cholesterol, sitosterol, and lovastatin on cholesterol absorption, biosynthesis, esterification, and LDL receptor function were examined in the rat jejunal mucosa. Cholesterol absorption was measured by the dual-isotope plasma ratio method; the rate-limiting enzyme of cholesterol biosynthesis, 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, was measured as total and expressed enzyme activities (in the absence and presence of a phosphatase inhibitor, NaF, respectively); mucosal total and esterified cholesterol concentrations were determined by gas-liquid chromatography; LDL receptor function was assayed as receptor-mediated binding of (125)I-labeled LDL to mucosal membranes. Feeding 2% sitosterol or 0.04% lovastatin for 1 week significantly (P < 0.01) decreased the amounts of cholesterol absorbed per day (-85% and -63%, respectively). In contrast, feeding 2% cholesterol for 1 week increased the amounts of absorbed cholesterol 27-fold, even though the percent absorption significantly decreased. With all three treatments, there was a coordinate regulation of total HMG-CoA reductase activity and receptor-mediated LDL binding. Cholesterol feeding downregulated both total jejunal HMG-CoA reductase activity (P < 0.05) and receptor-mediated LDL binding (P < 0.01), whereas lovastatin- and sitosterol-supplemented diets significantly upregulated both of these parameters. In the control, cholesterol-fed, and sitosterol-fed animals, about half of the total jejunal HMG-CoA reductase activity was expressed (in functional dephosphorylated form). However, in the lovastatin-treated rats with 4-fold stimulation of HMG-CoA reductase, only 23% of the total enzyme activity was expressed. Changes in total HMG-CoA reductase activity and receptor-mediated LDL binding in all tested groups occurred with no change in total concentrations of mucosal cholesterol, and only cholesterol-fed animals had increased mucosal esterified cholesterol concentrations. Thus, in response to various fluxes of dietary or newly formed cholesterol, HMG-CoA reductase and receptor-mediated LDL binding are coordinately regulated to maintain constant cellular cholesterol concentrations in the jejunum.     

Evaluation of the contribution of dietary cholesterol to hypercholesterolemia in diabetic rats and of sitosterol as a recovery standard for cholesterol absorption

The contribution of dietary cholesterol to hypercholesterolemia in diabetic rats fed chow ad libitum was evaluated. Diabetes was induced with streptozotocin, and the intake, absorption, and subsequent tissue distribution of dietary cholesterol were measured. Absorption was measured as the difference between [3H]cholesterol intake and fecal 3H-labeled neutral sterol excretion, using both [14C]sitosterol (added to diet) and [14C]cholesterol (added to feces) as recovery markers. [3H]Cholesterol absorption was underestimated by 1-3% using [14C]sitosterol as a recovery standard, due to the 7-8% absorption of sitosterol. After 3 weeks of diabetes, rats were hyperphagic, thereby increasing dietary cholesterol intake 2-fold. [3H]Cholesterol absorption was significantly increased from 69% in controls to 78% in diabetics, whereas [14C]sitosterol absorption was unaffected. With increased dietary cholesterol intake and decreased whole body cholesterol synthesis (Diabetes. 1983. 32: 811-819), influx from diet equaled for exceeded influx from synthesis. The amounts of 3H-labeled neutral sterol recovered from the small intestine, periphery, and plasma were increased 3- to 4-fold in the diabetic rats. Furthermore, the degree of hypercholesterolemia in diabetic rats was directly related to the fraction of plasma cholesterol derived from the diet. We conclude that the 2.3-fold increase in absorbed dietary cholesterol resulting from hyperphagia and, to a lesser extent, from increased fractional absorption, contributes to the hypercholesterolemia of diabetic rats fed chow ad libitum.     

Regulatory effects of dietary sterols and bile acids on rat intestinal HMG CoA reductase

The specific activity (concentration) of microsomal HMG CoA reductase of intestinal crypt cells was studied in rats fed sterols and bile acids, either singly or in combination. It was found that the basal activity of the reductase was not suppressed by the administration of relatively large amounts of bile acid (taurocholate or taurochenodeoxycholate). Bile acids reduced the specific activity of the reductase only in rats in which the activity of the enzyme had first been enhanced by biliary diversion or by sitosterol feeding. In addition, bile acid feeding abolished the diurnal elevation of reductase activity that normally occurs between midnight and 2 a.m. In no case did bile acids reduce enzyme activity below basal levels. A pronounced (60%) reduction of intestinal HMG CoA reductase activity was observed in rats fed cholesterol and bile acid in combination. This reduction in activity could not be ascribed to an increase in intestinal bile acid flux but was associated with an increase in sterol concentration within the intestinal crypt cells. These results indicate that dietary sterols and bile acids both play a role in the regulation of intestinal HMG CoA reductase.     

Discrimination between cholesterol and sitosterol for absorption in rats

The intestinal absorption of cholesterol and sitosterol was compared in rats. The intragastric administration of a single emulsified lipid meal containing either 50 mg of [4-14C]cholesterol or [4-14C]sitosterol resulted in the lymphatic absorption of 18.2% and 0.42% of each sterol, respectively, in 6 hr. This difference was unaltered when the mucosal sterol load was equalized by reducing the cholesterol to 1 mg in the emulsified lipid meal while maintaining the same sitosterol load or when the physical state in the lumen was equalized by infusion of a micellar solution containing both sterols into bile-diverted intestine. Lymphatic cholesterol was 90% esterified compared to 12% for sitosterol. Both sterols were associated predominantly (greater than 70%) with the chylomicron fraction. Eighty percent of the chylomicron cholesterol was recovered as ester with the core lipids, while 77% of the sitosterol was recovered as free sterol with the chylomicron coat. In mucosal homogenates at 6 hr, sitosterol recovery was one-eleventh that of cholesterol. When [3H]cholesterol (10 mg) and [14C]sitosterol (10 mg) were co-administered in an emulsified intragastric lipid meal, sitosterol associated with the brush border isolated 2 hr later was one-fifth that of cholesterol. Similar differences were seen when brush border membranes were incubated in vitro with micellar solutions containing either 50 microM [3H]cholesterol or [14C]sitosterol and the relative uptake of each sterol was unaffected by micellar phospholipid type (egg yolk phospholipids, phosphatidylcholine, or phosphatidylethanolamine).(ABSTRACT TRUNCATED AT 250 WORDS)     

Absorption and lymphatic transport of cholesterol in the rat

Rats with thoracic duct fistulae were fed triolein and triolein containing various amounts of labeled cholesterol. The analysis of the lymph lipids gave the following results. In the fasting state the cholesterol transported via the thoracic duct was 0.87 micromole/hr. Feeding 800 micromoles of triolein gave a maximum rate of transport of cholesterol of 1.65 micromoles/hr. Addition of cholesterol to the triolein further increased the cholesterol transport to a maximal rate of almost 5 micromoles/hr when 50 micromoles of cholesterol were fed per 800 micromoles of triolein. The exogenous fraction of the cholesterol transported increased linearly with increasing cholesterol load, constituting at the highest dose almost 90% of the total cholesterol transported. An almost constant fraction (about 0.4) of the dietary cholesterol was recovered in the thoracic duct lymph in 24 hr irrespective of the dose fed, from a trace up to 100 micromoles in 800 micromoles of triolein. Cholesterol absorption has the characteristics of a passive diffusion process.     

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.     

Micellar distribution of cholesterol and phytosterols after duodenal plant stanol ester infusion

Properties of the intestinal digestion of the dietary phytosterols, cholesterol and cholestanol, and the mechanisms by which phytosterols inhibit the intestinal absorption of cholesterol in healthy human subjects are poorly known. We have studied the hydrolysis of dietary plant sterol and stanol esters and their subsequent micellar solubilization by determining their concentrations in micellar and oil phases of the jejunal contents. Two liquid formulas with low (formula 1) and high (formula 2) plant stanol concentrations were infused via a nasogastric tube to the descending duodenum of 8 healthy human subjects, and intestinal contents were sampled for gas-liquid chromatographic sterol analysis 60 cm more distally. During the duodenal transit, phytosterol esters were hydrolyzed. This was especially profound for sitostanol, as its esterified fraction per milligram of sitosterol decreased 80% (P < 0.001) in formula 1 and 61% (P < 0.001) in formula 2. Contrary to that, esterified fraction of cholesterol per milligram of sitosterol was increased fourfold (P < 0.001) in formula 1 and almost sixfold (P < 0.001) in formula 2, whereas that of cholestanol remained unchanged. Percentages of esterified sterols and stanols in total intestinal fluid samples were higher after the administration of formula 2 than of formula 1. Esterified cholesterol and stanols accumulated in the oil phase, and free stanols replaced cholesterol in the micellar phase. At high intestinal plant stanol concentrations, cholesterol looses its micellar solubility possibly by replacement of its free fraction in the micellar phase by hydrolyzed plant stanols, which leads to a decreased intestinal absorption of cholesterol.     

Intestinal cholesterol absorption in the chyluria model

Isotopic methods for the measurement of dietary cholesterol absorption were compared with the lymph cholesterol balance procedure in filarial chyluria patients. After a single intravenous injection of radioactive cholesterol, absorption was found to be 746 +/- 136 mg/day by method I, which is based upon the fecal endogenous neutral steroid mass measurement, and 471 +/- 135 mg/day by the simultaneously measured lymph/plasma ratio of cholesterol specific activity (dpm/mg). The corresponding value, determined as the difference between lymph cholesterol transport on a cholesterol-containing diet (1500 mg) and on a cholesterol-free diet, was 622 mg/day. When radioactive cholesterol (1487 mg/day) was fed daily to a second patient, absorption determined by isotopic fecal recovery (353 mg/day) matched that obtained by the lymph balance procedure (326 mg/day). Transudation of plasma cholesterol into the intestinal lymph, estimated by the single intravenous injection of radioactive beta-sitosterol, was independent of both the luminal content of plant sterols and the absorption of dietary cholesterol. The absorption of endogenous cholesterol was calculated by: 1) subtracting the cholesterol originating from plasma (transudation) together with the absorbed dietary cholesterol found in lymph from the total mass of cholesterol transported in lymph, and 2) the lymph balance method, i.e., after interrupting the endogenous cholesterol mucosal uptake by beta-sitosterol feeding (9 g/day) while on a cholesterol-free diet. Endogenous cholesterol was preferentially absorbed compared to dietary cholesterol, but there was no competition for absorption. The major portion of dietary cholesterol found in lymph was esterified, but esterification was not a prerequisite for 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.     

Dietary intake of plant sterols stably increases plant sterol levels in the murine brain

Plant sterols such as sitosterol and campesterol are frequently administered as cholesterol-lowering supplements in food. Recently, it has been shown in mice that, in contrast to the structurally related cholesterol, circulating plant sterols can enter the brain. We questioned whether the accumulation of plant sterols in murine brain is reversible. After being fed a plant sterol ester-enriched diet for 6 weeks, C57BL/6NCrl mice displayed significantly increased concentrations of plant sterols in serum, liver, and brain by 2- to 3-fold. Blocking intestinal sterol uptake for the next 6 months while feeding the mice with a plant stanol ester-enriched diet resulted in strongly decreased plant sterol levels in serum and liver, without affecting brain plant sterol levels. Relative to plasma concentrations, brain levels of campesterol were higher than sitosterol, suggesting that campesterol traverses the blood-brain barrier more efficiently. In vitro experiments with brain endothelial cell cultures showed that campesterol crossed the blood-brain barrier more efficiently than sitosterol. We conclude that, over a 6-month period, plant sterol accumulation in murine brain is virtually irreversible.     

The selective uptake of cholesterol by the rat tapeworm Hymenolepis diminuta (Cestoda)

1. The sterols of Hymenolepis diminuta are almost exclusively cholesterol or similar C-27 sterols; the free sterols of its environment (the lumen of the rat intestine) are cholesterol and various phytosterols. 2. During incubation of tapeworms with mixed micelles of taurocholate, glyceryl monooleate, and equimolar [3H]cholesterol and [14C]beta-sitosterol, the uptake of cholesterol is 40 times more rapid than the uptake of sitosterol. 3. Following uptake, the desorption of labeled sitosterol is six times more rapid than that of cholesterol. 4. We did not detect the esterification of absorbed sterols or the conversion of absorbed sitosterol of cholesterol. 5. The highly selective uptake of cholesterol and the moderately selective desorption of phytosterols can account for the selective accumulation of C-27 sterol by the tapeworm.     

Quantification of cholesterol absorption in man by fecal analysis after the feeding of a single isotope-labeled meal

The fecal excretion of cholesterol-4-(14)C and -sitosterol-22,23-(3)H has been studied in normal human subjects after they had ingested a single meal containing the radioactive substances. When 150 mg of -sitosterol, dispersed in the butter of a standard breakfast, was fed to 20 subjects the mean recovery of isotope in the feces was 90%. When plant sterols (70% -sitosterol, 30% campesterol) were fed together with cholesterol and used as an internal standard to correct for losses of cholesterol during intestinal transit and analytical procedures, excretion of dietary cholesterol was found to be 60-80%, irrespective of the amount fed over the range 150-1910 mg. If absorption of cholesterol is calculated from these figures, no saturation of the cholesterol absorption mechanism is indicated for the amounts of cholesterol fed in this investigation. The reason for the differences between these findings and those previously reported by other procedures is not clear, but may be related to the acute administration of a single dose of cholesterol in this study.     

Dietary saturated fatty acid content affects lymph lipoproteins: studies in the rat

We examined effects on intestinal absorption of cholesterol and triglycerides and intestinal lipoprotein formation by feeding rats diets in which saturated fatty acids (palmitic plus stearic) comprised 78%, 68%, 48%, or 38% of triglyceride fatty acids. Absorption into lymph of radiolabeled cholesterol was proportional to triglyceride absorption. The rates of absorption of these lipids were related inversely to the % saturated fatty acids fed. The distribution of newly absorbed cholesterol and triglyceride into intestinal lipoproteins differed. With increasing cholesterol absorption more was recovered in very low density lipoproteins in contrast to the appearance preferentially in chylomicrons of larger quantities of fatty acid. Lymph lipid content did not reflect a consistent pattern in relation to the experimental diet fed. The fatty acid composition of triglyceride-rich lymph lipoproteins resembled the diet closely. One-quarter of the intestinal lymph particles from rats fed the highly saturated diets was flattened and polygonal as judged by electron microscopy if cooled to room temperature; whereas with the same diets, particles collected and isolated at 37 degrees C were round. Proportions of A-I and C apolipoproteins in triglyceride-rich intestinal particles varied inversely; apoA-I increased as fat/cholesterol absorption was greater. Diet-induced alterations in plasma lipoproteins and increased circulating triglycerides in this study in rats were unrelated to the variations in intestinal absorption or lymph lipoprotein formation.     

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.     

Sterol utilization in honey bees fed a synthetic diet: Analysis of prepupal sterols

The sterols of prepupal honey bees, Apis mellifera L., from brood reared by workers fed chemically-defined synthetic diets containing cholesterol, campesterol, sitosterol, stigmasterol, 24-methylenecholesterol, or no sterol over a 12-week period were isolated, identified, and quantified. The major sterol present in each prepupal sample was 24-methylenecholesterol, but significant levels of sitosterol and isofucosterol were also present in every case, as was a very small percentage of desmosterol (usually < 1%). This is the first report of isofucosterol being identified in the sterols of the honey bee. A considerably larger percentage of each dietary sterol was found in prepupae reared by workers fed that particular sterol in the diet. This was most dramatic in the case of the cholesterol diet in which case cholesterol content increased to as much as 17.2% of the prepupal sterols, whereas cholesterol had not exceeded 2.2% in samples from other diet regimens. However, stigmasterol comprised no more than 6.3% of the total sterols in any sample from prepupae fed the stigmasterol diet. The preponderance of 24-methylenecholesterol in all prepupae, regardless of the dietary sterol provided to the workers, as well as the lesser quantities of sitosterol and isofucosterol present in all samples, suggest a unique system of utilization and metabolism of these dietary sterols by the worker bees. Apparently they make available to the brood varying amounts of unchanged dietary sterol plus considerable and fairly constant portions of 24-methylenecholesterol, sitosterol, and isofucosterol drawn from their own sterol pools.     

Effects of endurance exercise training on markers of cholesterol absorption and synthesis

Abnormal cholesterol metabolism, including low intestinal cholesterol absorption and elevated synthesis, is prevalent in diabetes, obesity, hyperlipidemia, and the metabolic syndrome. Diet-induced weight loss improves cholesterol absorption in these populations, but it is not known if endurance exercise training also improves cholesterol homeostasis. To examine this, we measured circulating levels of campesterol, sitosterol, and lathosterol in 65 sedentary subjects (average age 59 years; with at least one metabolic syndrome risk factor) before and after 6 months of endurance exercise training. Campesterol and sitosterol are plant sterols that correlate with intestinal cholesterol absorption, while lathosterol is a marker of whole body cholesterol synthesis. Following the intervention, plant sterol levels were increased by 10% (p<0.05), but there was no change in plasma lathosterol. In addition, total and LDL-cholesterol were reduced by 0.16 mmol and 0.10 mmol, respectively (p<0.05), while HDL-C levels increased by 0.09 mmol (p<0.05). Furthermore, the change in plant sterols was positively correlated with the change in VO2max (r=0.310, p=0.004), independent of other metabolic syndrome risk factors. These data indicate that exercise training reduces plasma cholesterol despite increasing cholesterol absorption in subjects with metabolic syndrome risk factors.