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Biomedical subjects

M Keelan

Publications and source records attributed to M Keelan.

At least 73 records · Page 4Linked to original sources
PubMed1991

The irradiation-associated decline in the in vivo uptake of glucose observed in rats fed fish oil is prevented by feeding a diet enriched in saturated fatty acids.

Previous in vitro studies have shown that abdominal irradiation diminishes the uptake of many nutrients and that the extent of this effect can be modified by varying the type of dietary fatty acid. This study was undertaken to determine (1) the effect of dietary fish oil fatty acids (FO) on the in vivo absorption of D-glucose and (2) the effect of feeding isocaloric diets containing FO or beef tallow (BT) on the in vivo uptake of glucose 2 weeks after a single 600 cGy exposure to abdominal irradiation from a 137Cs source. Feeding FO reduced the jejunal and ileal maximal transport rate (Vmax) and Michaelis constant (Km) for glucose uptake in nonirradiated control animals. In irradiated rats the Vmax was higher and the Km was lower in animals fed BT than in those fed FO. The passive component of glucose uptake was higher in control rats fed FO than in those fed BT yet was lower in irradiated animals fed FO compared with those fed BT. Although the value of the Km fell with FO, the effective resistance of the intestinal unstirred water layer rose so that the uptake of lower concentrations of glucose was undisturbed. However, FO reduces the uptake of higher concentrations of glucose as a result of a decline in the value of the Vmax that is sufficiently large to override the enhanced passive permeability of the intestine to glucose.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdomen↗
PubMed1990

The physiology of adaptation to small bowel resection in the pig: an integrated study of morphological and functional changes.

This study examined the adaptive response to extensive small intestinal resection in the juvenile domestic pig. Control animals underwent an ileal transection with end-to-end anastomosis, whereas resected pigs had a resection of the mid-75% of the total small bowel length. Animals were followed for 16 weeks. Resected animals gained less weight than controls, with no significant difference in feed intake per unit animal weight. In vivo fat, protein, carbohydrate, and total energy absorption were reduced in resected animals. Resected pigs had increased in vitro passive ileal uptake of fatty acids, cholesterol, and L-glucose, but no change in active D-glucose uptake. Microscopic morphology was altered, with an increase in the size of villi, a decrease in villous density, and no net change in mucosal surface area per unit of serosal surface area. Gross bowel length and diameter increased proportionately more in the resected than the control groups. This study demonstrated that massive resection results in a significant change in nutritional status in the growing pig. Functional and morphological changes occur, demonstrating intestinal adaptation. These findings suggest that this model would be suitable for the study of therapeutic modalities for the short-bowel syndrome in humans.

Animals↗
PubMed1990

Intestinal microsomes: polyunsaturated fatty acid metabolism and regulation of enterocyte transport properties.

Recent evidence has suggested that transport of nutrients from the lumen to the interior of the gastrointestinal epithelium and exit of nutrients from the enterocyte to the circulation is governed by physicochemical properties of brush border and basolateral membranes, respectively. The main determinants of membrane properties are phospholipid, cholesterol, and fatty acyl chain composition (chain length and degree of unsaturation). Lipid synthesis occurs in enterocyte microsomes and the fine tuning of lipid composition is done at other subcellular sites by deacylation-reacylation or by changing the polar head group (e.g., by phosphatidylethanolamine methyltransferase). The present paper will focus on the mechanisms by which enterocyte membranes adapt functional properties in response to external stimuli. It is proposed that under the influence of internal or external stress, the enzymes of lipid metabolism in microsomes are modulated. These changes in lipid synthesis are reflected in other subcellular membranes, changing their physicochemical status and thus transport phenomena. One of the initial events appears to be alteration in desaturase enzyme activity. Our results suggest that desaturase activity and the fatty acyl profiles of the intestinal mucosal phospholipid rapidly respond to physiological conditions such as fasting and dietary fat treatment.

Animals↗
PubMed1990

Critical period programming of intestinal glucose transport via alterations in dietary fatty acid composition.

Intestinal adaptation occurs in response to physiological or pathological processes that include resection, aging, diabetes, radiation, lactation, chronic alcohol feeding, and feeding diets of varying lipid, protein, or carbohydrate composition. The mechanisms involved in the adaptive response include alterations in morphology, cell kinetics, digestive enzyme activity, transport, membrane lipid composition, and enzymes involved in lipid metabolism. This discussion will review the effect of aging and alterations in dietary fatty acid composition on the small intestine. In addition, it may be possible to program the intestinal response to aging by feeding diets of differing fatty acid composition during the critical period of weaning. Alterations in the ratio of polyunsaturated to saturated fatty acids in the diet modifies the age-associated changes in the intestinal uptake of glucose. The changes occur rapidly, progressively, and irreversibly, suggesting that the intestinal uptake of glucose is subject to critical period programming. The mechanism by which diet may modify the ability of the intestine to up- or down-regulate glucose transport requires further investigation.

Animals↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1989

Saturated fatty acid diet prevents radiation-associated decline in intestinal uptake.

Adult female Sprague-Dawley rats were fed isocaloric semipurified diets containing a high content of either polyunsaturated (P) or saturated (S) fatty acids; these diets were nutritionally adequate, providing for all known essential nutrient requirements. On day 3 after beginning S or P, one group of animals was exposed to a single 6-Gy dose of abdominal radiation, and the other half was sham irradiated. S or P diets were continued for a further 14 days. Brush-border membrane purification and sucrase-specific activities were unaffected by diet or by abdominal irradiation. In rats fed P, irradiation was associated with an increase in jejunal brush-border membrane total phospholipid and the ratio of phospholipid to cholesterol; these changes were not observed in animals fed S. In irradiated rats, ileal brush-border membrane phospholipid per cholesterol was high in animals fed S compared with P. In irradiated animals fed P, there was reduced jejunal and ileal uptake of several medium- and long-chain saturated and unsaturated fatty acids and cholesterol, and the ileal uptake of higher concentrations of glucose was reduced in irradiated animals fed P. In contrast, lipid uptake was similar in control and irradiated animals fed S except for cholesterol uptake, which was reduced. Ileal uptake of higher concentrations of glucose was increased in irradiated animals fed S. Quantitative autoradiography failed to demonstrate any change in the distribution of leucine or lysine transport sites along the villus 1 or 2 wk after abdominal irradiation or in response to feeding S or P. Also, these differences in transport achieved by feeding S to radiated animals were not explained by variations in the animals' food consumption or intestinal mucosal surface area. Thus the use of short-term feeding with a saturated fatty acid diet in the prevention of acute irradiation damage to the intestine warrants further investigation in humans.

Amino Acids↗
PubMed1989

Effect of oral enprostil, a synthetic prostaglandin E2, on intestinal brush border membrane lipid composition following abdominal irradiation in the rat.

Previous studies have demonstrated that external abdominal irradiation alters intestinal nutrient transport and brush border membrane (BBM) phospholipid content. This study was undertaken to assess the possible protective effect of oral dosing of enprostil, a synthetic E2 prostaglandin, on the BBM marker enzyme and lipid composition of non-irradiated control (CONT) animals and of rats exposed seven days perviously to a single dose of 600 cGy external abdominal irradiation (RAD). Half the CONT and RAD animals were orally dosed with enprostil 5 mcg/kg body weight, two and one mornings before the day of irradiation, and one hour before 600 cGy; the remaining half were dosed with placebo according to the same schedule. BBM were isolated and purified from the animals seven days post-irradiation for analysis of marker enzymes and lipid composition. Radiation was associated with a decline in jejunal and ileal BBM activity of sucrase. Enprostil was associated with a decline in the ratio of alkaline phosphatase/sucrase in jejunal BBM from irradiated rats, despite its preventing a radiation-associated decline in BBM sucrase activity. Radiation was associated with changes in ileal BBM phospholipids, and these alterations were not prevented with enprostil. Furthermore, enprostil given to non-radiated control rats altered BBM composition, such as increased jejunal and ileal lysophosphatidylethanolamine, and lowered ileal BBM sphingomyelin and phosphatidylethanolamine. Thus, enprostil failed to protect the intestine from the effects of abdominal irradiation on BBM phospholipids, but did partially prevent the effect of abdominal irradiation on jejunal sucrase activity.

Abdomen↗
PubMed1989

Improved intestinal form and function in diabetic rats fed long-term with a polyunsaturated fatty acid diet.

Short-term (two weeks) feeding of isocaloric diets supplemented with polyunsaturated fatty acids (PUFA) is useful for the prevention or treatment of the enhanced uptake of glucose which occurs in rats with streptozotocin-induced diabetes, as compared with animals fed a diet supplemented with saturated fatty acids (SFA). The study was undertaken to compare the effects of long-term (seven weeks) feeding PUFA or SFA to diabetic rats. We have previously reported that diabetic animals fed PUFA had superior body weight gain, lower hemoglobin AlC values, lower plasma cholesterol and triglyceride levels, lower percentage decline in glucose (K value) following intravenous glucose tolerance testing, near-normal values of hepatic microsomal glucose-6-phosphatase activity and near-normal concentrations of 18:2(6) and 20:4(6) in liver microsomal phosphatidylcholine and phosphatidylserine. However, jejunal and ileal uptake of varying concentrations of glucose were similar in the three diet groups. Thus, the potential long-term beneficial effects of feeding diets with a high PUFA/SFA ratio probably have their explanation in metabolic effects distant to their uptake by the intestine.

Animals↗