scholarly journals Disruption of retinoblastoma protein expression in the intestinal epithelium impairs lipid absorption

2014 ◽  
Vol 306 (10) ◽  
pp. G909-G915 ◽  
Author(s):  
Pamela M. Choi ◽  
Jun Guo ◽  
Christopher R. Erwin ◽  
Wambui S. Wandu ◽  
Jennifer A. Leinicke ◽  
...  
Keyword(s):  
Body Composition ◽  
Surface Area ◽  
Intestinal Epithelium ◽  
Retinoblastoma Protein ◽  
Mucosal Surface ◽  
Lipid Absorption ◽  
Fat Absorption ◽  
Functional Relationships ◽  
Intestinal Fat Absorption ◽  
Mucosal Surface Area

We previously demonstrated increased villus height following genetic deletion, or knockout, of retinoblastoma protein (Rb) in the intestinal epithelium (Rb-IKO). Here we determined the functional consequences of augmented mucosal growth on intestinal fat absorption and following a 50% small bowel resection (SBR). Mice with constitutively disrupted Rb expression in the intestinal epithelium (Rb-IKO) along with their floxed (wild-type, WT) littermates were placed on a high-fat diet (HFD, 42% kcal fat) for 54 wk. Mice were weighed weekly, and fat absorption, indirect calorimetry, and MRI body composition were measured. Rb-IKO mice were also subjected to a 50% SBR, followed by HFD feeding for 33 wk. In separate experiments, we examined intestinal fat absorption in mice with conditional (tamoxifen-inducible) intestinal Rb (inducible Rb-IKO) deletion. Microarray revealed that the transcriptional expression of lipid absorption/transport genes was significantly reduced in constitutive Rb-IKO mice. These mice demonstrated greater mucosal surface area yet manifested paradoxically impaired intestinal long-chain triglyceride absorption and decreased cholesterol absorption. Despite attenuated lipid absorption, there were no differences in metabolic rate, body composition, and weight gain in Rb-IKO and WT mice at baseline and following SBR. We also confirmed fat malabsorption in inducible Rb-IKO mice. We concluded that, despite an expanded mucosal surface area, Rb-IKO mice demonstrate impaired lipid absorption without compensatory alterations in energy homeostasis or body composition. These findings underscore the importance of delineating structural/functional relationships in the gut and suggest a previously unknown role for Rb in the regulation of intestinal lipid absorption.

Effect of normal microbial flora on intestinal surface area

1961 ◽  
Vol 201 (1) ◽  
pp. 175-178 ◽  
Author(s):  
Helmut A. Gordon ◽  
Edith Bruckner-Kardoss
Keyword(s):  
Small Intestine ◽  
Young Adult ◽  
Surface Area ◽  
Mucosal Surface ◽  
Microbial Flora ◽  
Mucosal Surface Area ◽  
Normal Microbial Flora

The mucosal surface area of the small intestine was determined in young adult, germfree and conventional rats. On the average, the germfree values were found to be 30% lower than those of conventional animals. This reduction was pronounced in the mid- and lower parts of the small intestine and relatively slight in the upper segment. It is assumed that the higher surface area values of conventional rats are due to the "physiologic" stimulation by the normal microbial flora.

Seasonal changes in gut morphology of the striped field mouse (Apodemus agrarius)

1995 ◽  
Vol 73 (6) ◽  
pp. 1095-1099 ◽  
Author(s):  
Anetta Borkowska
Keyword(s):  
Small Intestine ◽  
Surface Area ◽  
Seasonal Changes ◽  
Poor Quality ◽  
Mucosal Surface ◽  
Apodemus Agrarius ◽  
Late Autumn ◽  
Field Mice ◽  
Highly Correlated ◽  
Mucosal Surface Area

I studied seasonal changes in length and wet mass of the digestive tract and area of the mucosal surface of the small intestine in wild adult striped field mice (Apodemus agrarius). The length and mass of the gut varied with season in males but not females. The mucosal surface area of the small intestine was highly correlated with seasonal variations in the size of the alimentary tract. Changes in the surface area of the mucosa depended on changes in both villus size and the number of villi per unit area. The area of the intestinal mucosa varied during the year in both females and males, but unexpectedly, the mucosal surface area in females was significantly larger than in males only in autumn. Because gut size decreased toward late autumn, I suggest that late autumn was not a stressful period (i.e., because of low temperature or poor-quality food) for wild field mice. The decrease in gut parameters may have been an effect of declining metabolic requirements and completion of reproduction in late autumn.

Lack of protective effect of oral enprostil, a synthetic prostaglandin E2, on intestinal transport and morphology following abdominal irradiation in the rat

1989 ◽  
Vol 67 (10) ◽  
pp. 1351-1356 ◽  
Author(s):  
A. B. R. Thomson ◽  
M. Keelan ◽  
M. T. Clandinin ◽  
M. Tavernini ◽  
T. Lam ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Body Weight ◽  
Single Dose ◽  
Surface Area ◽  
Intestinal Transport ◽  
Mucosal Surface ◽  
The Other ◽  
Intestinal Uptake ◽  
Mucosal Surface Area ◽  
Abdominal Irradiation

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 μg/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. Enprostil had a different effect in RAD, with reduced jejunal uptake of FA 14:0; 16:0, 18:0, 18:3, and cholesterol and reduced ileal uptake of FA 16:0, 18:1, 18:2, 18:3, and cholesterol. Enprostil was associated with a reduced jejunal mucosal surface area in CONT and a reduced ileal mucosal surface area in RAD. The irradiation-associated decline in body weight was not observed in animals given enprostil despite the lack of change in food intake. The alterations in nutrient uptake were not due to differences in food intake, weight change, or mucosal surface area. Thus, enprostil given on three occasions just before a single dose of abdominal irradiation was associated with increased intestinal uptake of galactose, but failed to prevent most of the other irradiation-associated changes in active and passive intestinal transport, and accentuated rather than prevented the irradiation-associated diminution in mucosal surface area.Key words: adaptation, cholesterol, fatty acids, galactose, glucose, ileum, jejunum.

Dietary lipids modify the age-associated changes in intestinal uptake of fructose in rats

2005 ◽  
Vol 288 (1) ◽  
pp. G125-G134 ◽  
Author(s):  
L. Drozdowski ◽  
T. Woudstra ◽  
G. Wild ◽  
M. T. Clandinin ◽  
A. B. R. Thomson
Keyword(s):  
Fatty Acids ◽  
Surface Area ◽  
Saturated Fatty Acids ◽  
Dietary Lipid ◽  
Dietary Lipids ◽  
Mucosal Surface ◽  
Elderly Age ◽  
Old Rats ◽  
Mucosal Surface Area

Because reduced nutrient absorption may contribute to malnourishment in the elderly, age and diet modulate fructose uptake in mice, and alterations in fructose uptake may be paralleled by changes in the abundance of fructose transporters, the objectives of this study were to determine 1) the effects of aging on fructose absorption in rats, 2) the effect of feeding diets enriched with saturated fatty acids (SFA) vs. polyunsaturated fatty acids (PUFA), and 3) the mechanisms of these age-and diet-associated changes. Male Fischer 344 rats aged 1, 9, and 24 mo received isocaloric diets enriched with SFA or PUFA. The uptake of 14C-labeled d-fructose was determined in vitro using the intestinal sheet method. Northern and Western blot analyses and immunohistochemistry were used to determine the abundance of sodium-independent glucose and fructose transporters (GLUT)2 and GLUT5. When expressed on the basis of mucosal surface area, jejunal fructose uptake was increased in 9 and 24 mo compared with 1-mo-old animals fed SFA. PUFA-fed animals demonstrated increased fructose uptake at 24 mo compared with younger animals. Ileal fructose uptake was increased with SFA vs. PUFA in 9-mo-old rats but was reduced with SFA in 1- and 24-mo-old rats. Variations in GLUT2 and GLUT5 abundance did not parallel changes in uptake. These results indicate that 1) age increases fructose uptake when expressed on the basis of mucosal surface area, 2) age influences the adaptive response to dietary lipid modifications, and 3) alterations in fructose uptake are not explained by variations in GLUT2 or GLUT5.

Dietary effects of ω3-fatty acids on intestinal transport function

1988 ◽  
Vol 66 (7) ◽  
pp. 985-992 ◽  
Author(s):  
A. B. R. Thomson ◽  
M. Keelan ◽  
M. Garg ◽  
M. T. Clandinin
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Fish Oil ◽  
Surface Area ◽  
Body Weight Gain ◽  
Intestinal Transport ◽  
Mucosal Surface ◽  
Variable Effect ◽  
Ω3 Fatty Acids ◽  
Mucosal Surface Area

Animals were fed for 2 weeks on one of four isocaloric and isocholesterolic semisynthetic diets: high 18:3ω3, low 18:3ω3, high 20:5ω3, or low 20:5ω3. The weight of the intestine and the percentage of the wall consisting of mucosa was greater in high 20:5ω3 than in high 18:3ω3, and greater in low 20:5ω3 than in low 18:3ω3, although the mucosal surface area was 26% lower in high 20:5ω3 than high 18:3ω3. The jejunal uptake of 40 mM glucose and ileal uptake of 40 mM galactose was greater in high 18:3ω3 than in high 20:5ω3; jejunal uptake of fatty acid 12:0 was higher, but 18:0 was lower in high 18:3ω3 than in high 20:5ω3. The jejunal or ileal uptake of cholesterol was not affected by 20:5ω3. However, 20:5ω3 had a variable effect on the uptake of medium- and long-chain fatty acids. Alterations in the uptake of fatty acids and glucose were not explained by any difference in the animals' food consumption, body weight gain, or intestinal weight, but the reduced jejunal uptake of 40 mM glucose in rats fed the high 20:5ω3 diet was associated with reduced mucosal surface area. Thus, (i) varying the source of ω3-fatty acids (vegetable, 18:3ω3 versus fish oil, 20:5ω3) altered the mucosal mass of the intestine, and (ii) the source of the dietary ω3-fatty acid (18:3ω3 versus 20:5ω3) influenced intestinal hexose uptake, with fish oil having an anti-absorptive effect on the jejunal uptake of D-glucose.

Fish oil prevents effect of high cholesterol diet on active intestinal transport of galactose

1989 ◽  
Vol 67 (8) ◽  
pp. 829-836 ◽  
Author(s):  
A. B. R. Thomson ◽  
M. Keelan ◽  
M. L. Garg ◽  
M. T. Clandinin
Keyword(s):  
Fatty Acids ◽  
Fish Oil ◽  
Surface Area ◽  
Beef Tallow ◽  
Mucosal Surface ◽  
High Cholesterol Diet ◽  
Long Chain Fatty Acids ◽  
Mucosal Surface Area ◽  
Long Chain ◽  
Chain Fatty Acids

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.Key words: adaptation, dietary cholesterol, galactose, glucose, long-chain fatty acids, permeation, fish oil.

Water Flux Rates Across Dog Gallbladder Wall

1957 ◽  
Vol 191 (3) ◽  
pp. 555-560 ◽  
Author(s):  
Eugene Grim ◽  
Grafton A. Smith
Keyword(s):  
Urinary Bladder ◽  
Surface Area ◽  
Absorptive Capacity ◽  
Water Flux ◽  
Sodium Concentration ◽  
Gallbladder Wall ◽  
Mucosal Surface ◽  
Published Data ◽  
Gallbladder Mucosa ◽  
Mucosal Surface Area

Net and one-way flux rates of water across the dog gallbladder wall were measured by filling the organ with D2O enriched sodium chloride solutions of different osmotic activities and observing changes in volume and isotope concentration. Net flux rates out of the organ were found to be inversely proportional to the sodium concentration of the lumenal fluid, being 86 µl/min. at 70 mEq/l., zero at 220 mEq/l. and –121 at 421 mEq/l. One-way outflux rates decrease with increasing sodium concentration but not linearly; values of the order of 200–260 µl/min. were found. One-way influx rates are equal for hypotonic and isotonic solutions, but nearly double for hypertonic fluid. Comparison was made of water flux rates across the gallbladder wall with published data on dog ileum and urinary bladder, all appropriately corrected for mucosal surface area. On this basis, gallbladder mucosa seems to have the greatest absorptive capacity, and gallbladder and urinary bladder both seem to have greater permittivity to water than the ileum. The apparent higher water permittivity and absorptive capacity of ileum must be attributed to a much greater total mucosal surface area.

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

1991 ◽  
Vol 69 (5) ◽  
pp. 592-598 ◽  
Author(s):  
M. Keelan ◽  
A. B. R. Thomson
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Bile Acid ◽  
Food Intake ◽  
Bile Acids ◽  
Surface Area ◽  
Mucosal Surface ◽  
Intestinal Morphology ◽  
Restricted Diet ◽  
Mucosal Surface Area

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.Key words: active transport, adaptation, bile acids.

Expansion of intestinal stem cells associated with long-term adaptation following ileocecal resection in mice

2007 ◽  
Vol 293 (5) ◽  
pp. G1013-G1022 ◽  
Author(s):  
Christopher M. Dekaney ◽  
Jerry J. Fong ◽  
Rachael J. Rigby ◽  
P. Kay Lund ◽  
Susan J. Henning ◽  
...  
Keyword(s):  
Stem Cells ◽  
Flow Cytometry ◽  
Surface Area ◽  
Mucosal Surface ◽  
Intestinal Stem Cells ◽  
Brdu Incorporation ◽  
Ileocecal Resection ◽  
Crypt Fission ◽  
Mucosal Surface Area

Sustained increases in mucosal surface area occur in remaining bowel following massive intestinal loss. The mechanisms responsible for expanding and perpetuating this response are not presently understood. We hypothesized that an increase in the number of intestinal stem cells (ISC) occurs following intestinal resection and is an important component of the adaptive response in mice. This was assessed in the jejunum of mice 2–3 days, 4–5 days, 6–7 days, 2 wk, 6 wk, and 16 wk following ileocecal resection (ICR) or sham operation. Changes in ISC following ICR compared with sham resulted in increased crypt fission and were assayed by 1) putative ISC population (SP) by flow cytometry, 2) Musashi-1 immunohistochemistry, and 3) bromodeoxyuridine (BrdU) label retention. Observed early increases in crypt depth and villus height were not sustained 16 wk following operation. In contrast, long-term increases in intestinal caliber and overall number of crypts per circumference appear to account for the enhanced mucosal surface area following ICR. Flow cytometry demonstrated that significant increases in SP cells occur within 2–3 days following resection. By 7 days, ICR resulted in marked increases in crypt fission and Musashi-1 immunohistochemistry staining. Separate label-retention studies confirmed a 20-fold increase in BrdU incorporation 6 wk following ICR, confirming an overall increase in the number of ISC. These studies support that expansion of ISC occurs following ICR, leading to an overall increase number of crypts through a process of fission and intestinal dilation. Understanding the mechanism expanding ISCs may provide important insight into management of intestinal failure.

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