Patterns, mechanisms and signals for intestinal adaptation.
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Adaptation, Physiological↗
Biomedical subjects
A B Thomson
Publications and source records attributed to A B Thomson.
Acid secretion and acid suppression in pathogenesis and healing of peptic ulcer disease.
Numerous environmental and genetic factors have been implicated in the pathogenesis of peptic ulcer disease. Although the cause of this disorder has not been established, acid pepsin has been acknowledged at least as a permissive factor in its development. More important, inhibition of nocturnal or 24-hour intragastric acidity is predictably associated with ulcer healing. Famotidine 40 mg at bedtime maintains approximately one-third of pH readings at or above 3.5, reduces pepsin activity, and has no adverse effect on mean total serum gastric concentrations after one week of therapy. In addition, the effect of this dose of famotidine is comparable to ranitidine 300 mg at bedtime and predicts comparable rates of ulcer healing. Thus, monitoring of intragastric pH levels may be useful in identifying potent healers of peptic ulcer disease and in selecting optimal doses or timing of drug administration. Studies of famotidine using such measurements have suggested that this new H2-receptor antagonist is comparable to ranitidine in the healing of duodenal ulcers.
Anti-Ulcer Agents↗
Interactions of saturated, n-6 and n-3 polyunsaturated fatty acids to modulate arachidonic acid metabolism.
Anti-thrombotic effects of omega-3 (n-3) fatty acids are believed to be due to their ability to reduce arachidonic acid levels. Therefore, weanling rats were fed n-3 acids in the form of linseed oil (18:3n-3) or fish oil (containing 20:5n-3 and 22:6n-3) in diets containing high levels of either saturated fatty acids (hydrogenated beef tallow) or high levels of linoleic acid (safflower oil) for 4 weeks. The effect of diet on the rate-limiting enzyme of arachidonic acid biosynthesis (delta 6-desaturase) and on the lipid composition of hepatic microsomal membrane was determined. Both linseed oil- or fish oil-containing diets inhibited conversion of linoleic acid to gamma-linolenic acid. Inhibition was greater with fish oil than with linseed oil, only when fed with saturated fat. delta 6-Desaturase activity was not affected when n-3 fatty acids were fed with high levels of n-6 fatty acids. Arachidonic acid content of serum lipids and hepatic microsomal phospholipids was lower when n-3 fatty acids were fed in combination with beef tallow but not when fed with safflower oil. Similarly, n-3 fatty acids (18:3n-3, 20:5n-3, 22:5n-3, and 22:6n-3) accumulated to a greater extent when n-3 fatty acids were fed with beef tallow than with safflower oil. These observations indicate that the efficacy of n-3 fatty acids in reducing arachidonic acid level is dependent on the linoleic acid to saturated fatty acid ratio of the diet consumed.
Animals↗
Dietary fat saturation alters diabetic rat brush border membrane phospholipid fatty acid composition.
Alteration in dietary fatty acid composition produces changes in brush border membrane (BBM) fatty acid composition and changes in nutrient transport. Feeding a highly polyunsaturated fatty acid diet (P) reduces glucose uptake in diabetic rats to near control levels, whereas feeding a highly saturated fatty acid diet (S) enhances glucose uptake. Female Wistar rats were placed onto either a P or S diet for 5 weeks, injected with streptozotocin and continued on their respective diets for an additional 3 weeks. BBM were isolated, purified and extracted for analysis of fatty acyl constituents of phosphatidylcholine (PC) and phosphatidylethanolamine (PE). In jejunal and ileal BBM PC and PE, feeding S was associated with a decrease in total omega 6 fatty acids (18:2 omega 6), and an increase in the ratio of monounsaturated/saturated fatty acids as compared with animals fed P. In jejunal BBM PC and PE, the ratio of 18:2 omega 6/20:4 omega 6 was reduced in animals fed S as compared with those fed P. Diabetes was associated with fewer changes in BBM fatty acid composition in animals fed P as compared with those fed S. Feeding P to diabetic animals prevents the changes in BBM fatty acid composition observed when animals are fed S. Alterations in BBM lipid composition may be related to the enhanced permeability to glucose in animals fed S, while the similarity of BBM fatty acid composition in diabetic and control animals fed P may be related to the similar glucose uptake. The mechanisms controlling BBM lipid composition require further investigation, and may be important for the development of nutritional strategies for the control of diabetes.
Animals↗
Alterations in dietary fatty acid composition alter rat brush border membrane phospholipid fatty acid composition.
Female Wistar rats were fed for 8 weeks a high polyunsaturated fatty acid diet (P) enriched with 18:2w6 and 18:3w3, or a high saturated fatty acid diet (S) enriched with 16:0, 18:0 and 18:1w9. There was a similar jejunal BBM fatty acid profile in phosphatidylcholine (PC) and phosphatidylethanolamine (PE) composition in animals fed P. However, feeding S altered the fatty acid composition of BBM phospholipids: for PC, feeding S increased total monounsaturated fatty acids (e.g. 18:1(9)) and reduced total polyunsaturated fatty acids, especially the total w6 fatty acids. For PE, feeding S increased only the total monounsaturated fatty acids. The ratio of monounsaturated/saturated fatty acids was increased for PC and PE. Fatty acid changes were more pronounced in the jejunal than ileal BBM. It is concluded that alterations in dietary fatty acid saturation: (a) influences intestinal BBM phospholipid fatty acid composition; (b) these changes are quantitatively and qualitatively different for PC and PE; and (c) changes are greater in the proximal than in the distal intestine. It is proposed that the previously reported diet-associated changes in active and passive intestinal transport are due at least in part to these alterations in the fatty acid composition in brush border membrane phospholipids.
Animals↗
Dietary omega-3 fatty acids partially correct the enhanced in vivo uptake of glucose in diabetic rats.
This study was undertaken to determine the effects of feeding isocaloric semisynthetic diets high in saturated fatty acids from beef tallow (BT) or high in polyunsaturated fatty acids from fish oil (FO), on the clinical control and the in vivo uptake of varying concentrations of D-glucose into perfused jejunal and ileal loops of intestine of rats with streptozotocin diabetes. Jejunal and ileal weights were greater in diabetic than in control rats fed BT or FO, but the percentage of the intestinal wall comprised of mucosa was lower, resulting in a similar mass of mucosa in diabetic and in control animals. Feeding FO increased the jejunal unstirred water layer (UWL) resistance in control rats but decreased ileal UWL in diabetic animals; UWL was lower in diabetic than in control rats fed FO but was similar in those fed BT. The passive permeability coefficient (Pd) of the intestine for L-glucose was greater in diabetic than in control rats fed BT but not in those fed FO; Pd was higher in control rats fed FO than BT. The maximal transport rate (Vmax) and Michaelis constant (Km) of jejunal D-glucose uptake were lower in control rats fed FO than BT. Jejunal Vmax was lower in diabetic than control rats fed BT, yet was higher for those fed FO. The ileal Vmax for D-glucose uptake was greater in diabetic than in control animals fed BT or FO.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Long-term effects of manipulations of dietary omega-3 fatty acids on clinical control and in vitro uptake of glucose and lipids in diabetic rats.
The intestinal absorption of nutrients is increased in diabetic rats fed chow, yet short-term (two week) studies have demonstrated reduced and near-normal intestinal nutrient absorption in diabetic rats fed a diet high in polyunsaturated fatty acids. In this study we undertook to establish the effect of 10 weeks' feeding of isocaloric semisynthetic diets with high or low ratios of saturated (S)-to-omega-3 polyunsaturated (P) fatty acids ("fish oil") when given to streptozotocin diabetic rats. The fasting plasma glucose concentration was approximately 10% lower in diabetic rats fed P as compared with S, although the oral and intravenous glucose tolerance tests and the time-course of the oral and intravenous glucose-stimulated immunoreactive insulin levels were similar in P and S, as also were the levels of the hemoglobin A1C. The fasting plasma triglyceride concentrations were similar in P and S, but the fasting plasma cholesterol concentrations were approximately 20% lower in diabetic rats fed P as compared with S. Feeding P to diabetic animals was associated with a heavier intestine, which was comprised of a greater proportion of mucosal than submucosal tissue. The enhanced jejunal uptake of fatty acids 18:0 (stearic) and 18:2 (linoleic) as well as cholesterol observed in diabetic as compared with non-diabetic animals fed S was not observed in those fed P. The enhanced uptake of glucose in diabetic rats was also influenced by diet, with a lower rate for jejunal and ileal uptake of glucose in diabetic rats fed P than in those fed S.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Hypotriglyceridemic effect of dietary n - 3 fatty acids in rats fed low versus high levels of linoleic acid.
The effect of dietary alpha-linolenic acid (linseed oil) or eicosapentaenoic acid (fish oil) on serum and liver triacylglycerol levels in rats fed diets rich in saturated fatty acids (hydrogenated beef tallow) versus high in linoleic acid (safflower oil) was examined. Feeding fish oil with hydrogenated tallow lowered the serum triacylglycerol concentration while the combination of fish oil and safflower oil failed to do so. Inclusion of fish oil in the hydrogenated tallow diet lowered the triacylglycerol constant in level tissue whereas inclusion of linseed oil had no significant effect. Feeding of linseed oil or fish oil in the safflower oil diet resulted in lowering of the liver triacylglycerol levels. These results suggest that dietary fish oil may have greater hypotriglyceridemic effects in individuals/populations eating diets high in saturated fats compared with those consuming mainly polyunsaturated vegetable oils rich in n - 6 fatty acids.
Animals↗
Omega-3 fatty acids increase the arachidonic acid content of liver cholesterol ester and plasma triacylglycerol fractions in the rat.
Recent studies have demonstrated that dietary fish oils rich in eicosapentaenoic acid (C20:5,omega 3) lower the content of arachidonic acid and its metabolites in plasma and tissue phospholipids. The present study examined the fatty acid composition of cholesterol ester and triacylglycerol fractions from plasma and livers of rats fed diets enriched with saturated fatty acids (beef tallow), alpha-linolenic acid (linseed oil) or eicosapentaenoic acid (fish oil). Feeding diets containing linseed oil or fish oil for 28 days increased arachidonic acid (C20:4,omega 6) levels in the cholesterol ester fraction of liver and in the triacylglycerol fraction of the plasma lipids. Plasma cholesterol esters were depleted of C20:4,omega 6 after feeding of the diet containing either linseed oil or fish oil. The changes in C20:4,omega 6 content cannot be explained by alterations in cholesterol ester or triacylglycerol pools of plasma and liver. These results suggest that the decrease in phospholipid C20:4,omega 6 content generally observed after fish oil consumption may be partly due to a shift of C20:4,omega 6 from phospholipid to the triacylglycerol and/or cholesterol ester pools in the same tissue. Triacylglycerols and cholesterol esters may therefore play a buffering role in the homeostatic maintenance of tissue phospholipid levels of arachidonic acid.
Animals↗
Evidence for critical-period programming of intestinal transport function: variations in the dietary ratio of polyunsaturated to saturated fatty acids alters ontogeny of the rat intestine.
2-week isocaloric modifications in the dietary ratio of polyunsaturated/saturated fatty acids (P/S) alters intestinal transport in rats. This study was undertaken to test the hypotheses that (1) the fatty acid composition of a nutritionally adequate diet in early life has lasting consequences for active and passive intestinal transport processes; and (2) early life feeding experiences with diets of varying fatty acid composition influence the intestines' ability to adaptively up- or down-regulate intestinal transport in later life. Female Sprague-Dawley rats were weaned onto S or P and were maintained on these diets for 2, 10 or 12 weeks. An in vitro uptake technique was used in which the bulk phase was vigorously stirred to reduce the effective resistance of the intestinal unstirred water layer. P decreased and S increased the uptake of glucose, and this effect was progressive from 2 to 12 weeks. Switching from a P to an S diet decreased jejunal but increased ileal uptake of glucose, whereas switching from an S to a P diet was associated with a decline in both the jejunal and the ileal uptake of glucose. The ileal uptake of galactose increased as the animals grew on either P or S. Switching from P to S resulted in a decline in ileal uptake of galactose, whereas the opposite effect was observed when switching from S to P. The effect of feeding P or S on hexose uptake was influenced by the animals' dietary history: ileal glucose and galactose uptake was lower in animals fed P at an early age (PSP) than in animals fed P for the first time in later life (SSP). Jejunal glucose and galactose uptake was also lower in animals fed S at an early age (SPS) than in those fed S for the first time in later life (PPS). The alterations in the uptake of long-chain saturated and unsaturated fatty acids and cholesterol did not progress with longer periods of feeding, and in the jejunum, lipid uptake did not change when switching from P to S or S to P. Early feeding with P (PSP vs. SSP) was associated with lower jejunal uptake of 18:3 and lower ileal uptake of 12:0, whereas previous feeding with S (SPS vs. PPS) was associated with lower ileal uptake of cholesterol. The changes in uptake of hexoses and lipids was not explained by differences in the animals' food consumption, body or intestinal weight or mucosal surface area.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Influence of dietary fat composition on intestinal absorption in the rat.
Omega-3 fatty acids influence the function of the intestinal brush border membrane. For example, the omega-3 fatty acid eicosapentaenoic acid (20:5 omega 3) has an antiabsorptive effect on jejunal uptake of glucose. This study was undertaken to determine whether the effect of feeding alpha-linolenic acid (18:3 omega 3) or EPA plus docosahexaenoic acid (22:6 omega 3) on intestinal absorption of nutrients was influenced by the major source of dietary lipid, hydrogenated beef tallow or safflower oil. The in vitro intestinal uptake of glucose, fatty acids and cholesterol was examined in rats fed isocaloric diets for 2 weeks: beef tallow, beef tallow + linolenic acid, beef tallow + eicosapentaenoic acid/docosahexaenoic acid, safflower oil, safflower oil + linolenic acid, or safflower oil + eicosapentaenoic acid/docosahexaenoic acid. Eicosapentaenoic acid/docosahexaenoic acid reduced jejunal uptake of 10 and 20 mM glucose only when fed with beef tallow, and not when fed with safflower oil. Linolenic acid had no effect on glucose uptake, regardless of whether it was fed with beef tallow or safflower oil. The jejunal uptake a long-chain fatty acids (18:0, 18:2 omega 6, 18:3 omega 3, 20:4 omega 6, 20:5 omega 3 and 22:6 omega 3) and cholesterol was lower in safflower oil than with beef tallow. When eicosapentaenoic acid/docosahexaenoic acid was given with beef tallow (but not with safflower oil), there was lower uptake of 18:0, 20:5 omega 3 and cholesterol. The demonstration of the inhibitory effect of linolenic acid or eicosapentaenoic acid/docosahexaenoic acid on cholesterol uptake required the feeding of a saturated fatty acid diet (beef tallow).(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Fish oil prevents change in arachidonic acid and cholesterol content in rat caused by dietary cholesterol.
Rats were fed diets high in either saturated fat (beef tallow) or alpha-linolenic acid (linseed oil) or eicosapentaenoic and docosahexaenoic acids (fish oil) with or without 2% cholesterol supplementation. Consumption of linseed oil and fish oil diets for 28 days lowered arachidonic acid content of plasma, liver and heart phospholipids. Addition of 2% cholesterol to diets containing beef tallow or linseed oil lowered 20:4 omega 6 levels but failed to reduce 20:4 omega 6 levels when fed in combination with fish oil. Feeding omega 3 fatty acids lowered plasma cholesterol levels. Addition of 2% cholesterol to the beef tallow or linseed oil diet increased plasma cholesterol concentrations but not when fish oil was fed. Feeding the fish oil diet reduced the cholesterol content of liver, whereas feeding the linseed oil diet did not. Dietary cholesterol supplementation elevated the cholesterol concentration in liver in the order: linseed oil greater than beef tallow greater than fish oil (8.6-, 5.5-, 2.6-fold, respectively). Feeding fish oil and cholesterol apparently reduced 20:4 omega 6 levels in plasma and tissue lipids. Fish oil accentuates the 20:4 omega 6 lowering effect of dietary cholesterol and appears to prevent accumulation of cholesterol in plasma and tissue lipids under a high dietary load of cholesterol.
Animals↗
Dietary saturated fat level alters the competition between alpha-linolenic and linoleic acid.
Male weanling rats were fed semi-synthetic diets high in saturated fat (beef tallow) vs high in linoleic acid (safflower oil) with or without high levels of alpha-linolenic acid (linseed oil) for a period of 28 days. The effect of feeding these diets on cholesterol content and fatty acid composition of serum and liver lipids was examined. Feeding linseed oil with beef tallow or safflower oil had no significant effect on serum levels of cholesterol. Serum cholesterol concentration was higher in animals fed the safflower oil diet than in animals fed the beef tallow diet without linseed oil. Feeding linseed oil lowered the cholesterol content in liver tissue for all dietary treatments tested. Consumption of linseed oil reduced the arachidonic acid content with concomitant increase in linoleic acid in serum and liver lipid fractions only when fed in combination with beef tallow, but not when fed with safflower oil. Similarly, omega 3 fatty acids (18:3 omega 3, 20:5 omega 3, 22:5 omega 3, 22:6 omega 3) replaced omega 6 fatty acids (20:4 omega 6, 22:4 omega 6, 22:5 omega 6) in serum and liver lipid fractions to a greater extent when linseed oil was fed with beef tallow than with safflower oil. The results suggest that the dietary ratio of linoleic acid to saturated fatty acids or of 18:3 omega 3 to 18:2 omega 6 may be important to determine the cholesterol and arachidonic acid lowering effect of dietary alpha-linolenic acid.
Animals↗
A single night-time dose of famotidine is equivalent to ranitidine in decreasing 24-hour gastric acidity in asymptomatic duodenal ulcer subjects.
Six asymptomatic, non-smoking men with endoscopically proven duodenal ulcer disease received single nocturnal doses of placebo, 40 mg famotidine and 300 mg ranitidine each for 1 week prior to serial measurement of pH, peptic activity and serum gastrin concentrations over 24 h and of acid output. The intragastric pH fluctuated between 1.53 and 5.07 when subjects were given placebo but within 2 h of taking famotidine or ranitidine it rose to 5.57 or higher; the effect lasted for 12 h from midnight. Peptic activity fell during famotidine and ranitidine treatment and the decline was somewhat greater 8-15 h after using famotidine. Serum gastrin levels did not change materially with any treatment. The study shows the equivalent effect of standard bed-time doses of famotidine and ranitidine on intragastric pH, acid output and serum gastrin concentrations in asymptomatic men with duodenal ulcer disease.
Adult↗
Intestinal aspects of lipid absorption: in review.
The rapidly evolving field of lipid absorption is reviewed with the thrust of new knowledge focused on the interpendency of the luminal and cellular phases of absorption. To date little attention has been paid to factors that regulate the phospholipid biosynthesis in the enterocyte. The availability of 20:4 omega 6 may be the rate-limiting factor for phospholipid synthesis. The source of 20:4 omega 6 is unknown, whether it be synthesized de novo the enterocyte or entirely originating from degradation of bile phospholipid. It has been established that dietary fat can modulate the enterocyte membrane lipid composition and transport properties. Specified fats such as as fish oils rich in 20:5 omega 3 and 22:6 omega 3 have been implicated as protective against hypercholesterolemia. However, the effects of these dietary fats on the transport of nutrients across the enterocyte are not yet known, nor are the mechanisms responsible for the adaptive responses of the brush border identified.
Animals↗
Fish oil prevents effect of high cholesterol diet on active intestinal transport of galactose.
We tested the hypothesis that diets containing fish oils prevent the effects of a high cholesterol diet on the morphology and nutrient uptake of the intestine. Isocaloric semisynthetic diets were supplemented with beef tallow or fish oil containing low or high amounts of cholesterol and were fed to growing female Wistar rats for 14 days, after which the in vitro jejunal and ileal uptake of glucose, galactose, long-chain fatty acids, and cholesterol was determined. Feeding cholesterol with beef tallow was associated with a 12% decrease in the jejunal mucosal surface area. Feeding fish oil decreased jejunal mucosal surface area by 24%, as compared with the beef tallow diet, but the reduction was increased to 42% when fish oil and cholesterol were fed together. Ileal surface area was unaffected by varying the major source of dietary lipid, or by adding cholesterol. Despite the effect of fish oil on the mucosal surface area, the jejunal and ileal uptake of saturated as well as unsaturated long-chain fatty acids and cholesterol was similar in the four diet groups. Cholesterol supplementation enhanced the jejunal uptake of high concentrations of galactose only when fed with beef tallow, i.e., feeding fish oil prevented the enhancing effect of cholesterol on galactose uptake observed when beef tallow was fed. Thus, (i) a fish oil diet prevents the enhancing effect of cholesterol on jejunal active transport of galactose, an effect not explained by the reduction in jejunal mucosal surface area observed with the fish oil diet; (ii) these dietary manipulations result in a clear dissociation of the morphological from the transport adaptation of the intestine; and (iii) substitution of fish oil for beef tallow as the major source of lipid in the diet prevents the influence of cholesterol on the active intestinal transport of galactose.
Animals↗
Lack of protective effect of oral enprostil, a synthetic prostaglandin E2, on intestinal transport and morphology following abdominal irradiation in the rat.
Previous studies have demonstrated that abdominal irradiation alters intestinal uptake of nutrients. The purpose of this study was to determine the effect of an orally administered synthetic prostaglandin E2, enprostil, given on three occasions shortly prior to a single exposure to 600 cGy external abdominal irradiation, on intestinal active and passive transport processes and villus morphology measured 7 days later. Animals were sham-irradiated (CONT) or were exposed to a single dose of 600 cGy external abdominal irradiation (RAD); two and one mornings before the day of irradiation or sham irradiation, and 1 h before irradiation or sham irradiation enprostil was administered. One half of CONT and RAD groups were dosed orally with enprostil, 5 micrograms/kg body weight, and the other half of the CONT and RAD groups were dosed with placebo. Seven days later the in vitro uptake of glucose, galactose, long-chain fatty acids, and cholesterol was determined in the four groups (CONT with and without enprostil, and RAD with and without enprostil). In CONT, enprostil was associated with increased jejunal uptake of glucose and ileal uptake of galactose. In RAD given enprostil, there was increased jejunal uptake of galactose but reduced ileal uptake of glucose and galactose. The expected radiation-associated decline in jejunal galactose uptake was prevented with enprostil. In CONT given enprostil, there was increased jejunal uptake of fatty acid (FA) 14:0 and 16:0 but reduced uptake of FA 18:0, 18:1, and 18:2; enprostil had no effect on lipid uptake in the ileum in CONT.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Persistent impairment of endothelium-dependent relaxation to acetylcholine and progression of atherosclerosis following 6 weeks of cholesterol feeding in the rabbit.
The synthesis and (or) release of endothelium-dependent relaxant factor released by acetylcholine is impaired in New Zealand white rabbits fed an atherogenic diet. Experiments were designed to investigate whether the synthesis and (or) release of the endothelium-dependent relaxant factor from rabbit aortas are restored after reversal from an atherogenic diet to a non-atherogenic diet. Atherosclerosis was induced by feeding a diet containing lipids and 2% cholesterol for 6 weeks. Rabbits were sacrificed after 6 weeks on the atherogenic diet and 36 weeks after return to a standard laboratory diet. Synthesis and (or) release of the factor from the thoracic aorta was assayed using a bioassay system. The relaxant responses produced in the assay tissue were impaired both in the acute stage and after 36 weeks on non-atherogenic food. This impaired relaxation is probably due to a persistent functional abnormality in the aortic endothelium resulting in the failure to synthesize and (or) release endothelium-dependent relaxation factor 36 weeks after induction of atherosclerosis.
Acetylcholine↗