PubMed HealthSearch

Biomedical subjects

R J Jandacek

Publications and source records attributed to R J Jandacek.

At least 19 recordsLinked to original sources

Chylomicron triacylglycerol fatty acids in suckling northern elephant seals (Mirounga angustirostris) resemble the composition and the distribution of fatty acids in milk fat.

Following birth, the northern elephant seal (Mirounga angustirostris) pups rapidly gain weight by ingesting milk with a high fat content, as much as 50%. To better understand the metabolism of the pups during the suckling period, the positional distributions of triacylglycerol fatty acids in both the milk and chylomicra were determined. Extracts of enzymatically digested lipids were separated by thin layer chromatography and the constituent fatty acids were separated and quantified by gas liquid chromatography. Over 84% of the fatty acids were either monoenoic or saturated, with the ratio of monoenoic to saturated fatty acids ranging between 2.9-4.0. Positional distributional analyses revealed that the very long chain monoenoics (20:1 and 22:1) were located primarily at the sn-1,3 positions of milk triacylglycerols. In the interval between the onset of lactation to the time of weaning, the content of these very long chain monoenoic fatty acids at the sn-1,3 positions increased from 13-37%. At the sn-2 position, the percentage of 18:1 was 3-5-fold higher than 16:1. Analyses indicated that the triacylglycerols in both milk and suckling pup chylomicra were similar. This particularly was true for the distributions at the sn-2 position, indicating that milk fats are being absorbed primarily via the 2-monoacylglycerol pathway.

Animals

Relative effects on serum lipids and apolipoproteins of a caprenin-rich diet compared with diets rich in palm oil/palm-kernel oil or butter.

Two randomized, blind studies measured changes in serum cholesterol, other serum lipids, and apolipoprotein (apo) concentrations in hypercholesterolemic men consuming caprenin (Cap)-rich diets after either baseline diets enriched in palm oil/palm-kernel oil (PO/PKO) or butter. The triglyceride Cap contains 45% 22:0 and 50% 8:0-10:0. Compared with baseline values established at 3 wk on the PO/PKO diet, the 17 subjects on the Cap diet showed significant reductions after 6 wk in HDL cholesterol (HDL-C), HDL2-C, and HDL3-C and a significant increase in the ratio of total cholesterol, LDL-C, triglycerides, apo B-100, or apo A-I were seen. Compared with baseline values established at 3 wk on the butter diet, after 6 wk the seven subjects receiving the Cap diet showed no significant changes in the lipid and apolipoprotein indexes analyzed. These data show that one or more of 8:0, 10:0, and 22:0 fatty acids can contribute to hypercholesterolemia in men.

Adult

Positional analyses of triacylglycerol fatty acids in the milk fat of the antarctic fur seal (Arctocephalus gazella).

The positional distribution of fatty acids has been determined for the milk triacylglycerols of the Antarctic fur seal, Arctocephalus gazella. Of particular interest was the positional distribution of the polyunsaturated n-3 fatty acids in milk triacylglycerols (TG). In adipocytes of pinnipeds, TG are synthesized with the n-3 fatty acids primarily in the sn-1,3 positions. To determine the positional distribution, extracts of enzymatically digested lipids were separated by thin-layer chromatography, and the constituent fatty acids were separated and quantified by gas-liquid chromatography. Monoenoic and saturated fatty acids comprised over 75% of the total, the ratio of monoenoic to saturated fatty acids being 2:1. The percent content of the long-chain n-3 fatty acids, 20:5, 22:5 and 22:6, ranged between 15-20%. The positional analyses revealed that at the sn-2 position of milk TG, saturated fatty acids were in excess (57%), and the content of n-3 fatty acids was less than 5%. More than 80% of the n-3 fatty acids in milk were located in the sn-1,3 positions. The data indicate that in pinnipeds TG are synthesized in the mammary gland and adipose tissue with fatty acids having similar positional distributions.

Adipose Tissue

Distribution among tissues of intravenously administered sucrose octaoleate.

The distribution of [14C]oleate label in rat tissues in the 6 hr after intravenous administration of sucrose octa[14C]oleate (7.5 mg; SuO8) was compared with that observed after administration of [14C]triolein. The [14C]oleate label, whether injected as triolein emulsion, or as chylomicrons obtained from donor animals, rapidly cleared from the serum; only 10% or less remained in the serum 15 min after injection. Labeled SuO8 disappeared less rapidly from the serum; about one-third of the dose was present after 15 min, and after 120 min 14% remained. In the liver, there was an initial greater accumulation of fatty acid label when an emulsion of either triolein or SuO8 was given rather than the chylomicrons. The octaester continued to accumulate in the liver throughout the 6 hr of study, and 78% of the initial dose was present at that time. By contrast, although one-third of the triolein, as of SuO8, was found in the liver shortly after injection, levels subsequently decreased; at 6 hr, 12% of the label remained associated with that organ. A small portion, up to 8% of the acid label, whether administered as chylomicrons or as a triolein emulsion, was found in the epididymal fat pads. Smaller amounts, usually 1% or less, of the [14C]oleate label were found in fat pads following the injection of labeled SuO8. In a separate study, the levels of acid label in the liver and spleen were monitored for 21 days following the intravenous administration of [14C]SuO8. There was an initial accumulation of approximately half of the injected lipid label in the liver and one-quarter in the spleen. By day 21, the level in the liver had decreased to one-third of that administered, while the level in spleen remained at one-quarter.

Adipose Tissue

The excretion and characterization of intravenously administered olestra.

Although sucrose octaoleate that is consumed is neither digested or absorbed, following intravenous injection it is found mainly in the liver. Olestra is a mixture of the hexa-, hepta-, and octaesters of sucrose. To follow the metabolic fate of intravenously administered [14C]sucrose-labeled olestra, we measured its urinary elimination, and the rate of excretion of 14C in the feces, and characterized the 14C-labeled material that appeared in bile. The fecal excretion for days 4-14 after dosing was found to be first order with the half-life of the injected olestra being 5.0 +/- 0.5 days. The 14C recovered in the bile was soluble in chloroform. Two-dimensional thin-layer chromatography autoradiograms of the biliary lipid showed the pattern of the biliary 14C to be essentially the same as that of the dosed olestra. Biliary excretion and subsequent fecal egestion of essentially unhydrolyzed sucrose esters is the principal route for the removal of intravenously administered olestra. Only traces of 14C were found in the urine.

Adipose Tissue

Effects of partial replacement of dietary fat by olestra on dietary cholesterol absorption in man.

Olestra, a nonabsorbable fat substitute comprising long-chain fatty acid esters of sucrose, had been previously shown to reduce cholesterol absorption in humans when ingested at a level of 50 g/d. To determine whether or not a lower level of dietary olestra would also reduce cholesterol absorption, we studied the effect of 7 g of olestra twice a day in 20 normocholesterolemic male inpatients in a double-blind, crossover trial. Two 6-day diet treatment and stool collection periods were separated by a 14-day washout period. Half of the subjects received butter, and half, a butter-olestra blend during each treatment period according to a crossover design. All subjects ingested trace amounts of 3H-cholesterol and 14C-beta-sitosterol with the butter or the butter-olestra blend. Cholesterol absorption was determined from the 3H/14C ratios in the diet and in saponified and extracted stools according to previously validated methodology. Cholesterol absorption during the butter regimen was significantly greater than that during the olestra regimen (56.1% +/- 1.6% v 46.7% +/- 1.1%, P less than .01).

Adult

Reduction in the body content of DDE in the Mongolian gerbil treated with sucrose polyester and caloric restriction.

It has previously been shown that oral administration to rats of sucrose polyester (SPE4), a nonabsorbable lipophilic binding agent, greatly stimulates the fecal excretion of coorally administered DDT5 (R.J. Jandacek, 1982, Drug Metab. Rev., 13, 695-714). To determine whether this agent would stimulate the excretion of persistent metabolites of DDT stored in body tissues, we treated a group of gerbils with [14C]-DDT and monitored the fecal excretion of radioactivity for several months until a terminal, log-linear phase of excretion was observed. At this point, when greater than 75% of the fecal radioactivity was identified as [14C]DDE, we fed the animals diets containing up to 10% sucrose polyester and found that the rate of excretion of radioactivity in the stool promptly increased two to three times as compared to the rate in the preceding control period. Some rats were subjected to a 25-50% restriction in total food allotment, but this produced no significant change in fecal excretion of total radioactivity. However, when food restriction was combined with administration of sucrose polyester, there was a dramatic, eightfold average increase in excretion of fecal radioactivity. This synergistic effect was reversed (within 24 hr) when the animals were transferred to a normal diet. Measurement of total body radioactivity confirmed that food restriction plus sucrose polyester treatment reduced the body content of the pesticide. We conclude that stimulation of intestinal excretion may offer a new approach to treatment of patients exposed to lipophilic environmental contaminants.

Animals

The rapid hydrolysis and efficient absorption of triglycerides with octanoic acid in the 1 and 3 positions and long-chain fatty acid in the 2 position.

We describe rapid hydrolysis of triglycerides with medium-chain fatty acids in the 1 and 3 positions and a long-chain fatty acid in the 2 position. The triglycerides, 2-linoleoyl-1,3-dioctanoyl glycerol (8L8) and 2-oleoyl-1,3-dioctanoyl glycerol, hydrolyzed more rapidly than triglycerides comprising all long-chain fatty acids. The in vitro hydrolysis rate of 8L8 was similar to that of a medium-chain triglyceride of octanoic and decanoic acids in random positions. From intestinal recovery of 14C 45 min after injection into the isolated, irrigated loop of the small intestine of an anesthetized rat, the amount of 2-[1-14C]linoleoyl-1,3-dioctanoyl glycerol absorbed was greater than 2 1/2 times that of its long-chain analog, 2-[1-14C]linoleoyl-1,3-dioleoyl glycerol. These data support the ease of hydrolysis and absorption of 1,3-dioctanoyl triglycerides with long-chain fatty acids in the 2 position.

Animals

The effect of a non-absorbable fat on the turnover of plasma cholesterol in the rat.

Rats were injected with [4-14C]-cholesterol and then fed diets that contained sucrose polyester (SPE) at levels of 0 and 8% of the diet. 14C was measured in neutral and acidic steroid fractions of the feces collected during days 35-39 post i.v. injection. Periodic blood samples were used to measure the specific activity of the plasma cholesterol. The plasma data were consistent with a two-pool model for the decay of the plasma specific activity. The slow component of the decay curve decreased more rapidly in animals that received SPE. The half-life corresponding to this component was approximately 20% shorter in the SPE-fed animals compared to the control group. The mass of cholesterol calculated for the first pool was similar for all groups of animals. The 14C found in the feces was consistent with the more rapid removal of cholesterol from the body in the SPE-fed animals. The mass of excreted steroid was equal to the calculated rate of cholesterol production in each group of animals.

Animals

The substitution of sucrose polyester for dietary fat in obese, hypercholesterolemic outpatients.

Our aim was to determine the effects of the substitution of sucrose polyester (SPE) for dietary fat in a 16-week outpatient study in 36 obese subjects with primary hypercholesterolemia. The subjects were randomized into three groups who followed a 16-week treatment period where all subjects received hypocaloric diets which provided approximately 7 kcal/lb body weight, a polyunsaturated/saturated (P/S) fat ratio of 0.9, and 180 mg cholesterol/day. The percentages of calories as fat in the 3 groups were as follows: a low fat diet group (n = 12) received 27% of dietary calories as fat, a low fat plus SPE group (n = 13) received 25% of calories as fat plus 27 g SPE/day as a bread spread and salad dressing, and a third group (placebo, n = 11) received 37% of calories as fat with a 27 g/day conventional fat placebo (bread spread and salad dressing). Mean weight loss from baseline in the 16 week treatment period was 2.6, 3.9, and 3.4% respectively in the placebo, diet, and SPE groups, p less than .05 for each group, without significant differences between the groups. There was a mean reduction of low density lipoprotein cholesterol (LDL-C) of 16% in the SPE group (p less than .05), more than twice the reductions in the placebo and diet groups, 5% and 6%, respectively. There was a mean 20% reduction in the SPE group in triglyceride and very low density lipoprotein cholesterol (p less than .05), compared to 7 and 10% reductions in the placebo and diet groups respectively. The degree of weight loss was correlated with the degree of reduction in LDL-C in the low fat diet group, and in the low fat diet group plus SPE (r = 0.59 for both groups). Without confounding by different levels of dietary cholesterol or P/S, SPE induced significant reductions in LDL-C in hypercholesterolemic obese subjects beyond the effects of weight loss alone. The effects of SPE were significantly greater than those achieved by the use of a diet which severely limited conventional dietary fat intake (to 40 g/day). SPE in the form of a bread spread and a salad dressing is a practical formulation for outpatient hypocholesterolemic low fat diets and provides the lubricity and organoleptic benefits of authentic foods without the dense caloric content of digestible fats.

Adult

Studies with sucrose polyester.

Sucrose polyester (SPE) is a lipid synthesized from sucrose and fatty acid methyl esters. SPE has physical and organoleptic properties that closely resemble triglycerides, but it is not hydrolysed in the intestine and therefore not absorbed. By providing a persistent lipophilic phase in the intestine, SPE reduces the absorption of lipophilic substances such as cholesterol. SPE leaves the stomach more rapidly than triglyceride oils, presumably because of the absence of an effect on duodenal receptors. In studies with obese subjects, dietary SPE reduced total and LDL cholesterol by reducing the absorption of cholesterol from the intestine. In a study, in which SPE was covertly substituted for dietary fat, ten obese subjects in a weight-loss regimen did not increase dietary intake to compensate for the energy removed from the diet by SPE substitution. In a similar study with five naive, obese subjects, the investigators concluded that the mean energy intake decrease during SPE treatment [184 (769 kJ) kcal/d] was not significant. SPE continues to be studied as a means of reducing energy intake.

Cholesterol

A double-blind, placebo-controlled study of sucrose polyester in hypercholesterolemic outpatients.

Sucrose polyester (SPE) was studied in a double-blind, placebo-controlled trial in 91 outpatients with primary hypercholesterolemia. All patients maintained an isocaloric diet with cholesterol intake of 400 mg/day and a polyunsaturated to saturated fat ratio of 0.8 to 1.2 for the duration of the study. The study sequence consisted of a diet lead-in period, a first 8-wk treatment period, a 4-wk washout period, and a second 8-wk treatment period. Subjects were randomly assigned to six groups that differed by SPE dose (8, 16, and 32 g/day) and by the treatment period in which either SPE or an olive oil placebo was given in a bread spread formulation. Compared to placebo, the 8, 16, and 32 g/day doses of SPE decreased low-density lipoprotein cholesterol by 2%, 4% (p less than 0.05), and 5% (p less than 0.05) respectively, without changing high-density lipoprotein cholesterol. On SPE, 14/91 (15%) of the subjects experienced a decrease in low-density lipoprotein cholesterol greater than or equal to 10%, while only 2/91 (2%) showed this decrease with placebo.

Adult

Effect of sucrose polyester on fecal bile acid excretion and composition in normal men.

The effects of sucrose polyester (SPE) (a nonabsorbable mixture of hex-a, hepta,- and octa-fatty acid esters of sucrose with physical properties similar to those of common dietary fats) on fecal bile acid excretion and composition were assessed in 24 healthy, nonobese, normolipemic male volunteers, in a 40-day, inpatient, metabolic balance study. Isocaloric diets provided either 800, 300, or less than 50 mg of cholesterol/day (P/S ratios respectively 0.4, 1.0, and 1.5). After diet-only perids of 10 days (for the 800 and 300 mg cholesterol regimens), and 21 days (for the 50 mg diet), the diets were continued for 30 days, with addition of SPE to diets over three successive treatment periods of 10 days each, with 8, 16, and 35 g of liquid SPE/day, or 15, 30, and 50 g SPE/day in a SPE-hydrogenated palm oil mix. On both the liquid SPE and SPE-hydrogenated palm oil mix, there were no significant changes in fecal bile acid excretion as a function of dietary SPE, at any level of cholesterol intake, P > 0.1. In most subjects SPE changed fecal bile acid composition; lithocholic acid was decreased, and in most instances this was accompanied by the appearance and increase in chenodeoxycholic acid. In one subject, both deoxycholic and 3 beta, 12 alpha-dihydroxycholanic acid were reduced, with an accompanying increase in cholic acid. The hypocholesterolemic effect of SPE appears to be mediated through its reduction of intestinal absorption of cholesterol, not through effects on bile acid excretion.

Adult

Effect of an aqueous phase on the solubility of cholesterol in an oil phase.

In the absence of water, the solubility of cholesterol in triolein at 21 degrees C was 2.8%. When water was added to the system, the solubility of cholesterol in the oil phase decreased to 1.9%, and cholesterol monohydrate precipitated. The precipitation of the sterol evidently resulted from the excess concentration of the surface-active cholesterol at the interface, allowing the rapid interaction of water with cholesterol and the resulting formation of cholesterol monohydrate with its attendant lower energy and less soluble crystalline lattice. The ternary phase diagram for the system cholesterol--triolein--water, modified to include cholesterol monohydrate formation with the consequent decrease in sterol solubility; differs from the previously reported phase diagram. Other cholesterol--oil--aqueous systems related to biologically important lipids were studied. Cholesteryl oleate was more soluble than cholesterol in triolein (23% at 21 degrees C), and this value did not decrease when water was present. Water caused cholesterol to precipitate from cholesteryl linoleate at 37 degrees C. Thus crystalline cholesterol may be present in lipids found in atherosclerotic plaques at a lower concentration of free cholesterol than had been predicted previously. In another experiment, a micellar taurocholate solution precipitated cholesterol from triolein and from corn oil. These effects of aqueous systems suggest the possibility of cholesterol precipitation from dietary fat when it becomes mixed with water in the diet or stomach, or with the micellar phase in the intestine. Plant sterols were precipitated also from oil solutions by an aqueous phase. Water-induced sterol precipitation is a phenomenon that could occur in a variety of biological systems, and may be applicable to sterols in general.

Cholesterol

The effect of a nonabsorbable lipid, sucrose polyester, on the absorption of dietary cholesterol by the rat.

The absorption of cholesterol from diets containing various proportions of triglycerides and an unabsorbable fat, sucrose polyester (SPE), was determined in rats. Each replacement of 1% dietary triglyceride with SPE resulted in a 1.2% decrease in cholesterol absorption. The SPE was a mixture of the hexa-, hepta- and octa-esters of long chain fatty acids. The physical properties of this material are similar to those of the usual dietary triglycerides. Relative to these studies, cholesterol was found to be equally soluble in triolein or SPE. If water was present as well, the solubility of the sterol was decreased by the same amount in both fats. The distribution coefficients of cholesterol between an oil phase of either triolein or SPE and a micellar phase simulating that found in the lumen of the intestinal tract were identical. These two types of fats differ in that SPE is neither digested nor absorbed. The decrease in cholesterol absorption is attributed to the continued presence of an oil phase of SPE in the lumen of the intestine. Dietary cholesterol distributes itself between this oil phase and the micellar phase. That portion in the oil phase is not absorbed but is egested in the feces.

Animals