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Biomedical subjects

S B Clark

Publications and source records attributed to S B Clark.

54 records · Page 3Linked to original sources
PubMed1978

Chylomicron composition during duodenal triglyceride and lecithin infusion.

In lymph fistula rats infused intraduodenally with trioleoylglycerol emulsions, the secretion of triglyceride was enhanced and that of total and esterified cholesterol in chylomicrons was strikingly reduced when lecithin was added at 4-5 times the biliary lecithin secretion rate. During continued triglyceride secretion in the presence of lecithin, the phospholipid: unesterified cholesterol ratio of the chylomicrons increased significantly in contrast to lecithin-free emulsions. Bile-diverted lymph fistula rats secreted significantly less esterified and total cholesterol in lymph chylomicrons than controls, and the difference was magnified by lecithin administration. Cholesterol appears to become relatively unavailable for incorportion into chylomicrons when lecithin is administered at high rates.

Animals↗
PubMed1978

Intestinal lymph chylomicron cholesteryl ester during duodenal triolein infusion at increasing rate.

Chylomicron lipid composition in mesenteric lymph fistula rats was followed during duodenal triolein infusion at three rates. Esterified cholesterol decreased progressively in all groups as triglyceride transport continued, and the rate of decrease was reciprocally related to the triolein infusion rate. Suppression of cholesterol ester synthesis may spare unesterified cholesterol for chylomicron membrane formation. Ratios of triglyceride to phospholipid and to unesterified cholesterol increased with the duration of triglyceride secretion, while the chylomicron surface lipid composition remained constant over time. The rate of increase in the core:surface lipid ratios was the same irrespective of the triolein transport rate.

Animals↗
PubMed1977

The lecithin-cholesterol acyl transferase activity of rat intestinal lymph.

The lecithin-cholesterol acyl transferase (LCAT) activity in rat mesenteric lymph was examined as a possible source of chylomicron cholesteryl ester. Lymph activity was only 2-3% of rat serum activity. Removal of d less than 1.006 lipoproteins increased lymph LCAT activity, but only to 6-8% of that of serum. Relative to total cholesterol in the d greater than 1.08 g/ml fractions, lymph LCAT activity in lymph from fasting rats was less than serum, but in lymph from nonfasting rats the ratio LCAT/HDL-cholesterol reached levels greater than serum, suggesting a contribution of enzyme from the gut. Both LCAT activity and HDL concentration in mesenteric lymph increased during feeding. Subfractions of lymph that inhibited serum LCAT were: chylomicrons, VLDL, chylomicron lipid, VLDL apoprotein, and HDL apoprotein. In the rat, the low LCAT activity of mesenteric lymph was in part due to the low enzyme concentration present, and the activity was apparently lowered further by lipid-rich lipoproteins that inhibited the reaction. Enzyme inhibition due to the apoprotein fractions of lipoproteins is probably minor in the rat in vivo.

Acyltransferases↗
PubMed1976

Regulation of rat proximal intestinal glycolytic enzyme activity by ileal perfusion with glucose.

Specific activities of the glycolytic enzymes fructose-1-phosphate aldolase, fructose-1,6-diphophate aldolase, and pyruvate kinase, are higher in rat duodenum and jejunum than in ileum. Whether this gradient reflects the failure of dietary sugars to reach the ileum in high concentrations is unknown. Rats were first fed a carbohydrate-free diet for 3 days, which virtually removed the proximal-distal gradient of enzyme specific activities. Twenty percent glucose was then perfused directly into either the duodenum or the ileum for 3 days. Both proximal and distal glucose perfusion restored the normal gradient of all three enzymes. Ileal pyruvate kinase was also increased by ileal glucose perfusion, but ileal aldolases were no higher after distal perfusion than after duodenal perfusion. The low ileal aldolase levels normally found in fed rats therefore are an intrinsic property of distal intestine and are not due to failure of dietary sugar to reach this portion of the gut. Furthermore, adaptation of duodenal and jejunal glycolytic enzymes to ileal glucose perfusion suggests a humoral and/or neural mechanism rather than a direct local luminal effect of the sugar itself.

Animals↗
PubMed1975

Regional variation in glycolytic enzyme adaptation to dietary sugars in rat small intestine.

This investigation evaluated the adaptive response of the glycolytic enzymes, fructose-1-phosphate aldolase, fructose-1, 6-diphosphate aldolase, and pyruvate kinase, to dietary sugars throughout the small intestine. In addition, the effect of prior diet on this adaptive response and on the enzyme distribution pattern along the small intestine was studied. Rats were fed 40% glucose, 68% sucrose or carbohydrate-free diets for 6 days (baseline diet), followed by one of three isocaloric test diets (40% glucose, 68% sucrose or carbohydrate-free for 3 days. In other groups of tats isocaloric diets of 68% glucose, 68% fructose or 34% glucose + 34% fructose, fed for 4 days, were compared. Enzymes were assayed in the mucosa of the duodenum (D),and in 5 equal (by length) segments from the Ligament of Treitz to the ileocecal valve (J1, J2, J3, I1 and I2). Enzyme specific activities were significantly higher in the proximal (D-J1-J2) than distal segments (J3-I1-I2) on all diets (P smaller than 0.001). Enzyme activities after test diet periods were determined only by the test diet, and were independent of the baseline diet for all segments. The 68% carbohydrate diets increased enzyme activities significantly more (P smaller than 0.001) than the 40% glucose or carbohydrate free diets, in all segments. On the 40% glucose diet, activities were significantly higher (P smaller than 0.05) than on the carbohydrate free diet in D and J1, but not distally. The data suggest that there is an intrinsic gradient of enzyme activity from the proximal to the distal small intestine which persists despite dietary manipulation, and that all segments of the small bowel show adaptive increases to dietary sugars.

Aldehyde-Lyases↗
PubMed1975

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.

Animals↗
PubMed1974

Monoglyceride modification of jejunal absorption of fatty acid in the rat.

The effect of increasing the intracellular pool of monoolein upon the subsequent uptake and esterification of oleic acid was investigated using in vitro rat jejunal slice techniques. The mucosal pool of monoglyceride was expanded by preincubation of jejunal slices in a monoglyceride-containing bile salt medium at a temperature close to 1 degrees C, which inhibited esterification. Subsequent incubation in micellar [(14)C]oleic acid was performed either at 37 degrees C or in the cold. Monoglyceride preincubation increased [(14)C]oleic acid uptake by about 60% without increasing incorporation of fatty acid into triglyceride. This was not due to inhibition of esterifying capacity nor to changes in oleic acid binding to a mucosal fatty acid-binding protein. It is suggested that under these experimental conditions monoglyceride may modify intracellular pools of fatty acid. However, when monoglyceride and fatty acid were preincubated together, mucosal esterification rates during subsequent incubation at 37 degrees C more than doubled. Implications of these data for present theories of rate-limiting steps in lipid absorption are discussed.

Animals↗
PubMed1974

Polyenoic acid metabolism in cultured dissociated brain cells.

The incorporation of [1-(14)C]linolenate (18:3 n - 3) into cellular lipids of cultured dissociated brain cells was studied. During the initial phases of incubation, radioactivity was found in free fatty acids, diacylglycerols, triacylglycerols, and choline phosphoglyceride pools preferentially. Incorporation into the ethanolamine phosphoglyceride pool increased steadily and paralleled desaturation and chain elongation of 18:3 --> 20:3 --> 20:4 --> 20:5 --> 22:5 --> 22:6. From pulse-chase studies it was evident that the label of the highly polyunsaturated fatty acids in ethanolamine phosphoglycerides is constantly increased while the label in the fatty acids of choline phosphoglycerides decreased. Uptake of 18:3 by the cells was reduced by lowering incubation temperature, the triacylglycerol and ethanolamine phosphoglyceride pools being mainly affected. Lowering the incubation temperatures essentially abolished conversion of labeled 18:3 to the higher polyenoic acids. At intermediate temperatures, conversion of 18:3 to 20:5 n - 3 was still active, but conversion of 20:5 n - 3 to 22:6 n - 3 was abolished, suggesting that formation of 22:6 from 18:3 proceeds by at least two reactions distinguishable by their temperature dependency.

Animals↗
PubMed1973

Fat absorption in essential fatty acid deficiency: a model experimental approach to studies of the mechanism of fat malabsorption of unknown etiology.

Male rats were made deficient in essential fatty acids by feeding them a fat-free diet supplemented with 4% tripalmitin for 8-12 wk from the time of weaning. After feeding 0.5 ml of [(14)C]triolein or [(3)H]oleic acid, 72-hr stool recoveries of radioactivity were significantly greater in deficient rats than in chow-fed controls. Essential fatty acid deficiency did not reduce the absorptive capacities for triolein or for a medium-chain fat, trioctanoin, measured after 3 and 2 hr of maximal-rate duodenal infusion. In everted jejunal slices from essential fatty acid-deficient rats, uptake of micellar [(14)C]oleic acid at 0-1 degrees C was similar to that of controls, but the rate of incorporation of fatty acid into triglyceride after rewarming to 37 degrees C was significantly reduced. The specific activities of the microsomal esterifying enzymes, acyl CoA:monoglyceride acyltransferase and fatty acid CoA ligase in jejunal mucosa were 30% lower in essential fatty acid-deficient rats. However, the total microsomal enzyme activity adjusted to constant weight did not differ significantly in deficient rats compared with controls. After intraduodenal perfusion of triolein, accumulation of lipid in the intestinal wall was increased in the deficient rats. Because over 90% of the absorbed mucosal lipid was present as triglyceride, essential fatty acid deficiency appears to affect the synthesis or release of chylomicron lipid from the intestine. Analysis of regions of intestine showed that this delay in transport was most marked in the midportion of the small intestine.

Acyltransferases↗
PubMed1971

The uptake of oleic acid by rat small intestine: a comparison of methodologies.

The interaction between long-chain and medium-chain lipids during intestinal absorption was examined using several model systems. A decrease in steady-state triolein (LCT) output in thoracic duct lymph after addition of trioctanoin (MCT) to the duodenal infusion confirmed previous studies in unanesthetized rats which demonstrated inhibition of steady-state LCT uptake from the small intestinal lumen by MCT. In slices of everted rat jejunum octanoic acid reduced incorporation into triglyceride and initial uptake of (14)C-labeled oleic acid from micellar solutions. Inhibition of uptake did not occur at 0 degrees C, when triglyceride synthesis was blocked. Incubation of slices at low pH (5.8) or in the presence of dimethyl sulfoxide also reduced uptake of oleic acid and its incorporation into triglyceride. However, when everted sacs of jejunum were similarly incubated, octanoate, dimethyl sulfoxide, or low pH caused no inhibition of oleic acid uptake or esterification. The results indicate that the significance of kinetic data describing intestinal fatty acid absorption which were obtained from experiments conducted in vitro is highly questionable, and that suitable models for in vivo uptake kinetics have yet to be developed. However, analysis of the in vitro kinetic data suggests that the intestinal mucosal membrane does not function as a simple lipid interface with respect to fatty acid absorption.

Animals↗
PubMed1969

Inhibition of steady-state intestinal absorption of long-chain triglyceride by medium-chain triglyceride in the unanesthetized rat.

Maximal steady-state intestinal absorption rates in unanesthetized rats for triolein, a long-chain triglyceride, and for trioctanoin, a medium-chain triglyceride, are known to differ. Both these lipids are hydrolyzed in the intestinal lumen but the products of hydrolysis are metabolized differently by the mucosal cell. Intraduodenal infusion of trioctanoin was found to reduce steady-state triolein absorption. Luminal lipolysis was shown not to be rate-controlling. High rates of trioctanoin infusion significantly lowered the pH of the luminal aqueous phase and altered the partition of oleic acid between aqueous and oil phases. Two possible mechanisms for the inhibition of triolein uptake are considered. In the intestinal lumen medium chain lipids might have lowered the activity of oleic acid monomers in the aqueous phase and reduced passive diffusion into mucosal cells. Alternatively, competition between long and medium chain fatty acids for some common receptor during transport into the intestinal mucosal cell may have occurred. Despite significant inhibition of triolein absorption by high levels of trioctanoin, the maximum number of calories absorbed from mixtures of triglycerides exceeded the maxima from either glyceride alone. The optimum proportion of triolein to trioctanoin in lipid infusion mixtures was about 3:4 by weight and the optimum dosages about half maximal for each triglyceride, which represented a caloric intake of 4 kcal/rat per 2 hr. The absorption coefficient for this lipid mixture was about 90%. It is suggested that in patients who have a limited intestinal absorptive capacity dietary fat intake might be doubled with a caloric supplement of medium-chain triglycerides without increase in steatorrhea of long-chain fat.

Animals↗
PubMed1968

Rate-limiting steps in steady-state intestinal absorption of trioctanoin-1-14C. Effect of biliary and pancreatic flow diversion.

During continuous intraduodenal infusion of emulsified fat in rats, a steady state of intestinal absorption is achieved. Maximal steady-state absorption of trioctanoin, a medium-chain triglyceride (MCT), by unanesthetized, restrained rats was found to be the same after total bile diversion as in controls (1560 mumoles of fatty acid per hr).After pancreatic and bile diversion, absorption of MCT was still one-third as rapid as in controls, and mucosal uptake apparently occurred in the form of unhydrolyzed triglyceride. Returning bile to the intestinal lumen during pancreatic diversion did not increase the absorption rate.From intestinal tissue lipid-(14)C concentrations measured during steady-state maximal absorption it was possible to calculate turnover times for labeled lipid passing through the mucosal cells. Mucosal turnover times of about 4 min for control and bile-diverted rats, and about 20 min for animals with pancreatic diversion were obtained. The rate-limiting step in octanoic acid absorption in control and bile-diverted rats was probably mucosal penetration. During absorption of unhydrolyzed triglyceride by pancreatic flow-diverted rats, both passage from the lumen into the mucosal cell and intracellular lipolysis were rate-controlling factors.

Absorption↗