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Biomedical subjects

M Keelan

Publications and source records attributed to M Keelan.

At least 55 records · Page 3Linked to original sources

Role of a brush border membrane fatty acid binding protein in oleic acid uptake into rat and rabbit jejunal brush border membrane.

Oleic acid uptake was studied using adult rat and rabbit jejunal brush border membrane vesicles. The intestinal uptake of oleic acid is influenced by the activity of an amiloride-inhibitable brush border membrane Na+/H+ exchanger, NHE3: opposing Na+/H+ gradients (inward Na+ and outward H+ gradients) increased oleic acid uptake by about 40%, as compared with only an inward Na+ gradient, only an outward H+ gradient, or the absence of either Na+ or H+ gradients. This study was undertaken to test the hypothesis that a portion of oleic acid uptake is facilitated by a fatty acid binding protein in the brush border membrane (FABPPM) of adult rat jejunum. There was a reduction in the uptake of oleic acid when brush border membrane vesicles were incubated with a rat liver plasma membrane fatty acid binding protein antibody (anti-FABPPM-Ab) in the absence, but not in the presence, of opposing Na+/H+ gradients. Thus, oleic acid uptake occurs largely by partitioning of the lipid into the brush border membrane, as well as by a process which involves the activation of the brush border membrane Na+/H+ exchanger, and a membrane fatty acid binding protein.

Amiloride↗

Crypt cell production rate, enterocyte turnover time and appearance of transport along the jejunal villus of the rat.

Intestinal nutrient absorption is subject to adaptation with, for example, diabetes, diet lipid variations (isocaloric semisynthetic diets enriched with saturated (S) or polyunsaturated (P) fatty acids), ileal resection and abdominal irradiation. These models were used in rats to assess dynamic morphology and distribution of amino acid transporter along the villus. The enterocyte migration rate (EMR) was measured using [3H]thymidine; the vincristine metaphase arrest technique was used to determine the crypt cell production rate (CCPR); quantitative autoradiography was used to assess the time and age of enterocytes when the uptake of 1 and 20 mM [3H]leucine and [3H]lysine was initiated along the villus. The enhanced jejunal uptake of nutrients which occurs after a 50% distal enterectomy was associated with a fall in EMR and CCPR, yet the enhanced nutrient uptake which occurs in diabetes is not associated with any alteration in EMR, CCPR, enterocyte transport pool (ETP), i.e., the length of the enterocyte column along with the villus containing amino acid transporter) or expression of transporter along the villus. The reduced uptake of nutrients in rats fed P as compared with S was associated with increased rather than decreased ETP and age of the enterocytes at the tip of the villus. The reduced nutrient uptake which occurs 3 days after abdominal irradiation was associated with increased EMR and CCPR, and reduced ETP and age of enterocytes of the tip of the villus. However, 14 days after irradiation when nutrient transport remains reduced, these parameters have returned to normal. Thus, alterations in nutrient transport may be associated with changes in the dynamic morphology of the intestine, but the two processes are not necessarily interdependent. We speculate that the changes in the dynamic morphology of the intestine, and the changes of amino acid transport which occurs in these models of intestinal adaptation, are independently controlled.

Amino Acid Transport Systems↗

Dietary omega 3 fatty acids and cholesterol modify enterocyte microsomal membrane phospholipids, cholesterol content and phospholipid enzyme activities in diabetic rats.

Diabetes-associated changes in intestinal uptake of nutrients are modified by isocaloric variations in the type of dietary lipids, and are associated with alterations in the phospholipid and fatty acyl content of the intestinal brush border membrane. The present study was designed to test the hypothesis that diet- and diabetes-associated changes in enterocyte microsomal membrane phospholipids are due to variations in the activity of two phospholipid metabolizing enzymes, 1,2-diacylglycerol:CDPcholine cholinephosphotransferase (CPT) and phosphatidylethanolamine methyltransferase (PEMT). Adult female Wistar rats were fed one of four semisynthetic diets--beef tallow low in cholesterol (BT), beef tallow high in cholesterol (BTC), fish oil low in cholesterol (FO) or fish oil high in cholesterol. In half of the animals, diabetes mellitus was produced by injection of streptozotocin. Jejunal and ileal enterocyte microsomes (EMM) were isolated and analyzed for cholesterol and phospholipids, as well as for CPT and PEMT activities. In control animals, feeding FO reduced EMM total phospholipids including phosphatidylcholine (PC), phosphatidylethanolamine (PE) and phosphatidylinositol. Feeding FO resulted in a greater than 95% reduction in the activity of CPT. Diabetes was associated with increased jejunal EMM total phospholipids including sphingomyelin (SM) and PE, without associated changes in CPT or PEMT. Dietary cholesterol supplementation did not affect EMM total cholesterol or phosphlipid composition in control rats fed BT or FO, but was associated with an increase in EMM cholesterol in diabetic rats fed BT or FO. A decrease in total phospholipids due to a decline in SM, PC and PE in diabetic rats fed FO was not associated with changes in the activities of CPT or PEMT in EMM.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Feeding trans fatty acids to rats has no effect on the intestinal uptake of glucose, fatty acids or cholesterol.

Trans fatty acids are produced in the manufacture of margarine, and these hydrogenated fatty acids may have a deleterious effect on the reduction in fasting levels of serum cholesterol anticipated from the feeding of cis polyunsaturated fatty acids. We undertook this study in rats to test the effect of feeding trans fatty acids on the intestinal uptake of glucose, fatty acids and cholesterol. Adult female Wistar rats were fed for 2 weeks semisynthetic, isocaloric diets containing no oleic acid (18:1), cis 18:1 or trans 18:1. There was no difference between the three dietary groups in the animals' food consumption or body weight gain. Rats fed trans 18:1 had an approximately 20% decline in the total weight of the ileum as compared with controls fed no 18:1, and therefore there was also a decline in the percentage of the ileal tissue comprised of mucosa. When comparing rats fed trans 18:1 with those fed cis 18:1 or no 18:1, there was no difference in the uptake of varying concentrations of D-glucose when expressed as nmol.100 mg tissue-1.min-1 or nmol.100 mg mucosal-1.min-1 for jejunum or for ileum. Also, there was no difference in the value of the maximal transport rate (Vmax), Michaelis constant (Km), or the contribution of passive uptake of glucose assessed with L-glucose. There was no diet-associated change in the jejunal or ileal uptake of a medium-chain length fatty acid (lauric acid), a long-chain length saturated fatty acid (palmitic acid), a monounsaturated fatty acid (oleic acid), two polyunsaturated fatty acids (linoleic and linolenic acids), or cholesterol. Thus, we conclude that 2 weeks' feeding of trans fatty acid to rats has no influence on the jejunal or ileal uptake of glucose, fatty acids or cholesterol.

Absorption↗

Dietary omega-3 fatty acids and cholesterol modify desaturase activities and fatty acyl constituents of rat intestinal brush border and microsomal membranes of diabetic rats.

The diabetes-associated changes in intestinal uptake of nutrients are modified by isocaloric alterations in the type of dietary lipids, and is associated with alterations in the phospholipid and fatty acyl content of the intestinal brush border membrane. We wished to test the hypothesis that diet- and diabetes-associated changes in brush border membrane phospholipid fatty acids are due to alterations in the activity of enterocyte microsomal delta-5, delta-6 and delta-9 desaturases. Adult female Wistar rats were divided into two groups. In half of the animals, diabetes was produced with the injection of streptozotocin, and the other half of the animals served as nondiabetic controls. Both groups were raised on chow for two weeks and were then randomized to one of four semisynthetic diets for two weeks: beef tallow low in cholesterol (BT), beef tallow high in cholesterol (BTC), fish oil low in cholesterol (FO), or fish oil high in cholesterol (FOC). Feeding a high cholesterol diet increased the activity of jejunal enterocyte microsomal membrane activity of delta-5 and delta-9-desaturases when fed with FO in non-diabetic control rats, increased delta-5-desaturase in diabetic rats fed FO, and increased the ileal activity of delta-5 and delta-6-desaturases in control and diabetic animals fed FO. Dietary fatty acids, cholesterol and diabetes did not produce the changes in the amount of fatty acids in BBM phosphatidylcholine or phosphatidylethanolamine expected from the measured alterations in delta-5 (20:4 omega 6 and 20:5 omega 3), in delta-6 (18:3 omega 6 and 18:4 omega 3), or in delta-9 desaturase (18:1 omega 9 and 16:1 omega 7). In summary, 1) the activities of enterocyte microsomal membrane delta-5, delta-6 and delta-9-desaturases are independently influenced by dietary fatty acids or cholesterol, or by diabetes; 2) changes in dietary fatty acids, cholesterol and diabetes are associated with alterations in the fatty acyl constituents of brush border membrane phosphatidylcholine and phosphatidylethanolamine, but these fatty acyl changes are not explained on the basis of variations in the activities of the microsomal desaturases. Thus, the intestinal brush border membrane and the enterocyte microsomal desaturases are capable of adapting in response to changes in dietary lipids or diabetes, but the two alterations are not necessarily causally interrelated.

Animals↗

Feeding an isocaloric omega-3 fatty acid diet reduces the brush border membrane vesicle uptake of glucose in streptozotocin-diabetic rats.

Glucose uptake is increased into the intestine of diabetic rats, and this adaptation can be modified further by manipulation of the type of fatty acids in the triglycerides in the diet. Jejunal brush border membrane vesicles were used to examine the uptake of D-glucose into the jejunum of non-diabetic control and streptozotocin-diabetic rats fed for two weeks in isocaloric semisynthetic diet enriched with saturated fat (beef tallow) or polyunsaturated omega-3 fatty acids (fish oil). The time-course of uptake of 100 microM glucose demonstrated an overshoot which peaked at approximately 30 seconds and declined thereafter to an equilibrium plateau. In concentration studies, glucose uptake was greater into brush border membrane vesicles of diabetic as compared with control rats. The maximal transport rate (Vmax) was increased approximately 9-fold in diabetics as compared with control rats fed beef tallow (p < 0.05), and was increased approximately 6-fold in diabetic rats fed fish oil. In diabetic rats, feeding fish oil reduced the value of the Vmax by approximately 50% as compared with diabetic rats fed beef tallow. Thus, the enhanced glucose uptake into BBM vesicles of streptozotocin-diabetic rats can be partially corrected by feeding an isocaloric semisynthetic diet enriched with polyunsaturated omega-3 fish oils.

Animals↗

Delayed effects of early nutrition with cholesterol plus saturated or polyunsaturated fatty acids on intestinal morphology and transport function in the rat.

This study was undertaken to test the hypotheses that: (1) the fatty acid and/or cholesterol composition of a nutritionally adequate isocaloric semisynthetic diet given in early life has lasting consequences for intestinal nutrient uptake and morphology; and (2) early life feeding experiences with diets of varying fatty acid or cholesterol composition influence the ability of the intestine to adapt to an altered nutrient uptake in later life. Weanling female Sprague-Dawley rats were fed nutritionally adequate isocaloric semisynthetic diets enriched with beef tallow, beef tallow plus 1% cholesterol, fish oil or fish oil plus 1% cholesterol. Animals fed fish oil or fish oil plus cholesterol for 11 weeks had a lower food intake but greater weight gain than animals fed beef tallow or beef tallow plus cholesterol. The age of the animals influenced lipid and hexose uptake. The uptake of these nutrients could also be changed by the addition of cholesterol to the diet. This cholesterol-related effect depended on the type of fat in the diet (saturated vs. polyunsaturated). These changes in nutrient uptake were associated with but not necessarily explained by alterations in food intake, body weight gain, intestinal mucosal weight or surface area. Finally, these changes in nutrient uptake and morphology may or may not be reversible. We speculate that dietary lipids may affect the ability of the intestine to adapt to an altered nutrient intake in later life.

Adaptation, Physiological↗

Different mechanisms of uptake of stearic acid and cholesterol into rabbit jejunal brush border membrane vesicles.

The rate of uptake of stearic acid and cholesterol solubilized in taurocholic acid (TC) was examined in rabbit jejunal brush border membrane vesicles (BBMV). For stearic acid (18:0) or cholesterol there was an initial rapid rate of uptake, which reached a plateau within approximately 1 min and remained stable thereafter. At low concentrations of 18:0 and 20 mM, but not 2 mM, TC, there was a curvilinear relationship between the concentration of 18:0 and uptake, whereas the relationship between cholesterol uptake and concentration was linear over a wide range of values. When the concentration of TC was held constant at increasing concentrations of 18:0 or cholesterol, there was a linear increase in the rate of uptake. When the concentration of 18:0 or cholesterol was held constant and the concentration of TC was increased from 2 to 20 mM, the uptake of 18:0 declined, but the rate of uptake of cholesterol increased. When the concentrations of 18:0 plus TC, or cholesterol plus TC, were both increased in unison and their ratio was held constant, their rate of uptake increased. Thus, (i) BBMV may be used to assess the rate of uptake of lipids; (ii) the partitioning of cholesterol from bile acid micelles into the BBMV appears to be by way of "collision" of the cholesterol with the membrane. In contrast, the uptake of 18:0 from the micelle into the membrane vesicles may be by both the collision and the aqueous/dissociation models; and (iii) 18:0 uptake may be mediated by both a concentration-dependent and a concentration-independent component.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Lipid absorption: passing through the unstirred layers, brush-border membrane, and beyond.

Lipids are components of our diet and luminal secretions, with physicochemical characteristics that determine their digestion and absorption in the gastrointestinal tract. Lipids include triglycerides, phospholipids, and cholesterol. Dietary lipids contain approximately 97% triglycerides, with small amounts of phospholipids and cholesterol. These components are important in cell membrane composition, fluidity, peroxidation, prostaglandin and leukotriene synthesis, and cellular metabolic processes. Lipids are implicated in the mechanisms of brain development, inflammatory processes, atherosclerosis, carcinogenesis, aging, and cell renewal. Duodenal hydrolysis of dietary lipids and biliary phospholipids and cholesterol is carried out by pancreatic lipase, colipase, phospholipase A2, and cholesterol esterase. Bile acid solubilization results in mixed micelles and liposomes, in gel and liquid crystal phases. Lipid digestion products pass across the intestinal unstirred water layer. For long-chain fatty acids and cholesterol, passage across the unstirred water layer is rate limiting, whereas passage of short- and medium-chain fatty acids is limited by the brush-border membrane. Within the unstirred water layer, an acidic microclimate aids micellar dissociation so that protonated, and to a lesser extent, nonprotonated monomers then pass across the intestinal brush-border membrane. Absorptive mechanisms have been studied extensively in relation to lipid composition, fatty acid chain length, degree of unsaturation, essential fatty acid content, phospholipid components, and cholesterol. Enterocytes may take up lipids from the intestinal lumen or from lipoproteins of the bloodstream, but these pools are likely to be functionally distinct. Recent advances are reviewed, including recent advances in the area of microclimates, compartmentation, lipid binding proteins, intracellular trafficking, intestinal lipoproteins, release of lipids across the basolateral membrane, and dietary effects.

Bile Acids and Salts↗

Fish oil modifies effect of high cholesterol diet on intestinal absorption in diabetic rats.

Omega-3 fatty acids ('fish oil') reduce the intestinal absorption of glucose and lipids in normal and in diabetic rats, but their effect is altered by the presence of saturated or poly-unsaturated omega-6 fatty acids in the diet. This study was undertaken to test the hypothesis that the influence of fish oil on the intestinal uptake of nutrients in diabetic rats is also influenced by the cholesterol content of the diet. Streptozotocin diabetic rats were raised for 2 wk on semisynthetic diets in which the lipid composition was derived mainly from beef tallow (BT), beef tallow plus cholesterol (BTC), fish oil (FO), or fish oil plus cholesterol (FOC). Food intake and weight gain was similar in the 4 diet groups, although the fasting blood glucose was lowest in diabetic rats fed BT. Cholesterol supplementation increased intestinal wall and mucosal weights when fed with BT, but the opposite effect was seen with FO, with lower wall and mucosal mass with FOC than with FO. Ileal uptake of D-glucose was lower in FO than in BT or FOC. Cholesterol feeding was associated with enhanced jejunal uptake of cholesterol when fed with BT, but the converse was observed with FO. Thus, 1) the reduction of glucose absorption associated with feeding fish oil is blunted in the presence of a supplemented intake of cholesterol; and 2) a fish oil diet reduces cholesterol uptake even in the presence of a high level of dietary cholesterol. It remains to be established what is the optimal ratio of dietary saturated, polyunsaturated omega-3 and omega-6 fatty acids, and cholesterol required to normalize intestinal transport function in diabetic rats.

Animals↗

Desaturation of linoleic acid in the small bowel is increased by short-term fasting and by dietary content of linoleic acid.

The rate of desaturation of linoleic acid (18:2(n - 6)) and level of arachidonic acid (20: 4(n - 6)) in mucosal microsomes from small intestine of rats fasted for 24 h or fed diets of different fatty acid composition was examined. Fasting or feeding a diet high in linoleic acid increased delta 6-desaturase activity, a rate-limiting enzyme in the arachidonic acid biosynthetic pathway in the jejunum. After fasting, delta 6-desaturase activity was also enhanced in the ileum. Feeding a diet rich in n - 3 fatty acids had no significant effect on delta 6-desaturase activity in jejunal or ileal mucosal microsomes. Following fasting, arachidonic acid content of microsomal total phospholipids increased in the jejunum with a concomitant decrease in linoleic acid content. Arachidonic acid and 18:2(n - 6) concentration remained unchanged in ileal microsomes after short-term food withdrawal. Feeding a diet containing n - 3 fatty acids lowered the content of 20:4(n - 6) and increased 20:5(n - 3) and 22:6(n - 3) levels in both jejunal and ileal microsomes. These data indicate that the level of 20:4(n - 6) and the biosynthesis of 20:4(n - 6) by desaturation-chain elongation of 18:2(n - 6) in the rat enterocyte responds rapidly to change in physiological conditions such as fasting and dietary fat composition.

Animals↗

Characterization of lipid intake into rabbit jejunal brush border membrane vesicles.

The absorption of lipids is generally accepted to be mediated by a process of passive diffusion, although some recent data have raised the possibility of a mediated component. Brush border membrane vesicles (BBMV) have been widely used to study nutrient transport, but have only recently been used to examine the uptake of lipids. Using a BBMV technique validated with studies of the uptake of D-glucose, we examined the uptake of linoleic acid into the jejunum of adult rabbits. The uptake of 100 microM linoleic acid was constant between 2 and 20 min, with no overshoot observed at earlier periods. Linoleic acid uptake was suppressed by 88% with 0.6 mM phloridzin and by 58% with 0.2 mM phloretin, but uptake of linoleic acid was unaffected by the absence of sodium, by the presence of a sodium gradient, or by varying the osmolarity of the buffer. Lysis of the BBMV incubated with linoleic acid by the addition of ice-cold deionized water did not alter the amount of linoleic acid associated with the BBMV. The linoleic acid concentration curve was linear up to 160 microM, when carried out under initial rate conditions and in the presence of 2 mM taurocholic acid. These results are compatible with the process of passive uptake of linoleic acid into BBMV of rabbit jejunum, but do not exclude the possible physiological importance of a membrane fatty acid binding protein.

Animals↗

Two weeks of oral synthetic E2 prostaglandin (Enprostil) improves the intestinal morphological but not the absorptive response in the rat to abdominal irradiation.

Enprostil, a synthetic E2 prostaglandin, was administered in a dose of 5 micrograms/kg body weight by gastric tube to rats for 14 days following abdominal irradiation with a single dose of 600 cGy from a 137Cs source. Enprostil prevented the body weight loss and the reduced food intake observed in irradiated animals given placebo, and also prevented the irradiation-associated decline in the mucosal weight and surface area of the ileum. Enprostil given to nonirradiated animals reduced the maximal transport rate (Vmax) and the apparent Michaelis constant (Km*) for the ileal uptake of D-glucose, but did not prevent the irradiation-associated decline in the ileal uptake of glucose. Thus, there is a dissociation of the effects of Enprostil on the morphological and the absorptive properties of the intestine. It is concluded that a 2-week course of a daily oral dose of E2 prostaglandin begun shortly after a single exposure to nonlethal abdominal irradiation prevents the radiation-associated reduction in the intestinal mucosal surface area and the animal's body weight, but does not prevent the malabsorption of glucose.

Animals↗

Dietary lipid content influences the clinical and intestinal adaptive responses to islet transplantation in diabetic rats.

Nutrient absorption is increased in rats with streptozotocin-induced diabetes mellitus (DM). This intestinal adaptive response is modified by isocaloric manipulations of the dietary content of fatty acids, and separate studies have shown a normalization of the enhanced uptake of glucose and lipids when DM rats are treated with transplantation of 3000 syngeneic pancreatic islets of Langerhans. These studies were undertaken to test the hypothesis that modification of the type of fatty acids in the triglycerides in isocaloric semisynthetic diets (S, saturated fatty acids from beeftallow; or F, polyunsaturated fatty acids from fish oil) fed to DM recipients influences the ability of syngeneic transplanted islets to normalize the clinical indices of glycemic control and the intestinal adaptive response. A suboptimal number of islets was transplanted (1200) under the renal capsule, so that the clinical parameters of diabetic control would be modestly abnormal and so that any possible beneficial influence of this dietary manipulation might better be able to demonstrate a further improvement of clinical endpoints. Adult Male Wistar-Furth rats were rendered diabetic, transplanted with 1200 syngeneic islets, and were then fed for 6 weeks a chow or a isocaloric semisynthetic diet enriched with either S or F. Islet transplantation reduced the diabetes-associated abnormalities in food consumption, body weight gain, intestinal weight, urine glucose concentrations, urine volume, oral glucose tolerance, hemoglobin A1c and blood urea nitrogen concentration; these changes were all similar in transplanted animals fed S, F, or chow. Plasma concentrations of cholesterol and triglycerides were significantly elevated in transplanted rats fed S as compared to those fed F or chow. Transplanted DM rats had reduced in vitro intestinal uptake of stearic, oleic, linoleic and linolenic fatty acids, and cholesterol as compared with untreated DM rats, but the uptake of lipids was similar in transplanted DM rats fed S, F, or chow diets. Feeding rats S prevented the decline in the value of the jejunal maximal transport rate (Vmax) and apparent Michaelis affinity constant (Km) observed in transplanted DM rats fed F, but the lack of difference in glycemic control in transplanted DM rats fed F was likely due to their higher ileal Vmax for glucose uptake. Thus, intestinal adaptive function and clinical glycemic control are influenced by the type of fatty acids fed to syngeneic islet-transplanted DM rats.

Animals↗

Feeding rats a diet enriched with saturated fatty acids prevents the inhibitory effects of acute and chronic ethanol exposure on the in vitro uptake of hexoses and lipids.

Chow-fed rats were given 15% ethanol in their drinking water for 4 weeks, and then for the next 2 weeks of ethanol exposure they were fed isocaloric semisynthetic diets enriched in either saturated (S) or polyunsaturated (P, linoleic acid) fats. Food intake was lower in ethanol-fed (ETH) than in control (C) rats, but the average body weight gain was similar in ETH and C fed S or P. Intestinal dry weight and the percentage of the intestinal wall comprised of mucosa were more than 2-fold higher in ETH than C fed P, whereas these values were 50% lower in ETH than C fed S. The in vitro jejunal uptake of glucose and galactose was higher in ETH than C fed S, whereas the converse was true when feeding P. These effects were due to differences in the values of the maximal transport rate (Vmax), the Michaelis constant (Km), and the contribution of passive permeation. The relative permeability of the intestine to lipids was unchanged by giving ethanol or by feeding S or P, but the individual rates of uptake of most medium- and long-chain fatty acids and cholesterol were lower in ETH fed P as compared with S. In a second series of studies the acute effect of ethanol exposure was examined: animals were fed S or P for 2 weeks and the intestine was then removed: when 5% ethanol was added directly to the test solutions, there was lower in vitro jejunal and ileal uptake of glucose and higher jejunal uptake of 18:2 when rats were previously fed P, but not in those fed S. In summary; (1) feeding an isocaloric polyunsaturated fatty acid diet has a trophic effect on the intestinal mucosa of animals chronically drinking ethanol; and (2) feeding rats a diet enriched with saturated fatty acids prevents the inhibitory effects of acute and chronic ethanol exposure on the in vitro jejunal uptake of glucose, galactose and lipids observed in animals fed a polyunsaturated diet. Thus, the effect of chronic consumption of ethanol on the active and passive jejunal uptake of nutrients is influenced by the type of lipids in the animal's diet.

Alcoholism↗

Feeding diets containing 2% cheno- or urso-deoxycholic acid or cholestyramine to rats for two weeks alters intestinal morphology and bile acid absorption.

This study was undertaken to examine the effect of supplementing chow for 2 weeks with 2% cheno- (CDC) or ursodeoxycholic (UDC) acid or cholestyramine (CHOL) on the intestinal morphology and in vitro uptake of bile acids in adult rats. Food intake was higher in UDC and CHOL as compared with animals fed chow or CDC, or in animals pair-fed a chow-restricted diet (CRD). Body weight gain was lower in CDC and CRD but was unchanged by feeding UDC or CHOL. Jejunal mucosal surface area was similar in the five groups, although the ileal mucosal surface area was lower in UDC than in the other animals. Feeding UDC reduced the ileal uptake of cholic acid (C), taurocholic acid (TC), and glycocholic acid (GC). Feeding CDC had no effect on bile acid uptake except when compared with animals fed a chow-restricted diet. Feeding CHOL reduced the active ileal uptake of C, had no effect on the uptake of TC or GC or CDC, and was associated with increased uptake of stearic, linoleic, and linolenic acids. These effects were likely related to a direct effect of changes in the luminal bile acids rather than due to an indirect effect of the reduced food intake, since the ileal uptake of CDC and GC was greater in animals fed CDC than in those fed a chow-restricted diet with comparable weight gain. Thus, 2 weeks of feeding bile acids or bile acid binding agents may alter the form and function of the rat intestine, and as well may lead to changes in food intake and body weight gain.

Animals↗

Isocaloric modification of dietary lipids influences intestinal brush border membrane composition in diabetic rats.

Variations in the dietary fatty acid composition and cholesterol content are associated with alterations in the intestinal uptake of hexoses and lipids in control and diabetic rats. Changes in the composition of the brush membrane (BBM) lipids may provide a possible mechanism for the observed alterations in transport properties. Accordingly, control and streptozotocin diabetic animals were fed one of four isocaloric semisynthetic diets for two weeks: beef tallow with low cholesterol, beef tallow with high cholesterol, fish oil with low cholesterol or fish oil with high cholesterol. BBM were prepared and assessed for marker enzyme activity and lipid composition. Fish oil feeding was associated with a reduction in total phospholipid content in control and diabetic jejunal and ileal BBM; this fall in total phospholipids was due to a reduction in BBM sphingomyelin. Cholesterol supplementation increased control jejunal BBM sucrase activity in animals fed beef tallow but reduced sucrase activity in animals fed fish oil. In fish oil fed diabetic animals, jejunal and ileal BBM alkaline phosphatase activity was increased with cholesterol supplementation. The elevation in BBM total phospholipids (phosphatidylethanolamine) associated with diabetes in beef tallow fed animals was not observed in the jejunal BBM of animals fed fish oil or in the ileal BBM of animals fed fish oil with high cholesterol. Thus, (a) feeding an omega-3 polyunsaturated fatty acid diet (fish oil) reduced total phospholipid content in BBM of control and diabetic animals, primarily due to a reduction in sphingomyelin; and (b) feeding an omega-3 polyunsaturated fatty acid diet or dietary cholesterol supplementation alter the activity of BBM enzymes. These results suggest that variations in dietary fat composition and the associated changes in BBM composition and enzyme activity contribute to altered intestinal function in diabetes.

Animals↗