551 Regulation of Intestinal Villus Cell Brush Border Membrane Bile Acid Co-Transport in Obesity

2016 ◽  
Vol 150 (4) ◽  
pp. S116
Author(s):  
Subha Arthur ◽  
Ibrahim Mohammed ◽  
Balasubramanian Palaniappan ◽  
Soudamani Singh ◽  
Uma Sundaram
Keyword(s):  
Bile Acid ◽  
Brush Border ◽  
Brush Border Membrane ◽  
Intestinal Villus ◽  
Villus Cell

scholarly journals Mechanism of Dyslipidemia in Obesity—Unique Regulation of Ileal Villus Cell Brush Border Membrane Sodium–Bile Acid Cotransport

Cells ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 1197 ◽  
Author(s):  
Sundaram ◽  
Palaniappan ◽  
Nepal ◽  
Chaffins ◽  
Sundaram ◽  
...  
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Brush Border ◽  
Dietary Fat ◽  
Brush Border Membrane ◽  
Farnesoid X Receptor ◽  
Bile Acid Absorption ◽  
Associated Proteins ◽  
Villus Cell ◽  
Stimulation Of

In obesity, increased absorption of dietary fat contributes to altered lipid homeostasis. In turn, dyslipidemia of obesity leads to many of the complications of obesity. Bile acids are necessary for the absorption of dietary fat. In the mammalian intestine, apical sodium-dependent bile acid cotransporter (ASBT; SLC10A2) is exclusively responsible for the reabsorption of bile acids in the terminal ileum. In rat and mice models of obesity and importantly in obese humans, ASBT was increased in ileal villus cells. The mechanism of stimulation of ASBT was secondary to an increase in ASBT expression in villus cell brush border membrane. The stimulation of ASBT was not secondary to the altered Na-extruding capacity of villus cells during obesity. Further, increased Farnesoid X receptor (FXR) expression in villus cells during obesity likely mediated the increase in ASBT. Moreover, enhanced FXR expression increased the expression of bile-acid-associated proteins (IBABP and OSTα) that are responsible for handling bile acids absorbed via ASBT in villus cells during obesity. Thus, this study demonstrated that in an epidemic condition, obesity, the dyslipidemia that leads to many of the complications of the condition, may, at least in part, be due to deregulation of intestinal bile acid absorption.

scholarly journals Identification and characterization of rabbit small intestinal villus cell brush border membrane Na-glutamine cotransporter

2008 ◽  
Vol 295 (1) ◽  
pp. G7-G15 ◽  
Author(s):  
Jamilur R. Talukder ◽  
Ramesh Kekuda ◽  
Prosenjit Saha ◽  
Subha Arthur ◽  
Uma Sundaram
Keyword(s):  
Small Intestine ◽  
Amino Acid ◽  
Brush Border ◽  
Brush Border Membrane ◽  
Intestinal Villus ◽  
Villus Cell ◽  
Small Intestinal ◽  
Small Intestinal Villus ◽  
Glutamine Uptake

Glutamine, the primary metabolic fuel for the mammalian small intestinal enterocytes, is primarily assimilated by Na-amino acid cotransporters. Although Na-solute cotransport has been shown to exist in the brush border membrane (BBM) of the absorptive villus cells, the identity of Na-glutamine cotransport in rabbit small intestinal villus cells was unknown. Na-dependent glutamine uptake is present in villus BBM vesicles. An intravesicular proton gradient did not stimulate this Na-dependent glutamine uptake, whereas Li+ did not significantly suppress this uptake. These observations in concert with amino acid substitution studies suggested that Na-glutamine cotransporter in the villus cell BBM was the newly identified cotransporter B0AT1 (SLC6A19). Quantitative real-time PCR identified the message for this cotransporter in villus cells. Thus a full-length cDNA of B0AT1 was cloned and expressed in MDA-MB-231 cells. This expressed cotransporter exhibited characteristics similar to those observed in villus cells from the rabbit small intestine. Antibody was generated for B0AT1 that demonstrated the presence of this cotransporter protein in the villus cell BBM. Kinetic studies defined the kinetic parameters of this cotransporter. Thus this study describes the identification, cloning, and characterization of the Na-amino acid cotransporter responsible for the assimilation of a critical amino acid by the absorptive villus cells in the mammalian small intestine.

scholarly journals Bile Acid Malabsorption in Cystic Fibrosis; Membrane Vesicles, a Tool for Revealing the Role of the Ileal Brush Border Membrane

1985 ◽  
Vol 74 (s317) ◽  
pp. 28-30 ◽  
Author(s):  
F. W. M. ROOIJ ◽  
J. W. O. BERG ◽  
M. SINAASAPPEL ◽  
E. P. BOSMAN-JACOBS ◽  
A. C. TOUW-BLOMMESTEIJN
Keyword(s):  
Cystic Fibrosis ◽  
Bile Acid ◽  
Brush Border ◽  
Brush Border Membrane ◽  
Membrane Vesicles ◽  
Bile Acid Malabsorption

Ontogeny of bile acid transport in brush border membrane vesicles from rat ileum

1986 ◽  
Vol 90 (5) ◽  
pp. 1188-1196 ◽  
Author(s):  
M.Susan Moyer ◽  
James E. Heubi ◽  
Anita L. Goodrich ◽  
William F. Balistreri ◽  
Frederick J. Suchy
Keyword(s):  
Bile Acid ◽  
Brush Border ◽  
Brush Border Membrane ◽  
Membrane Vesicles ◽  
Brush Border Membrane Vesicles ◽  
Acid Transport ◽  
Rat Ileum ◽  
Bile Acid Transport

scholarly journals Radiation-inactivation analysis of the Na+/bile acid co-transport system from rabbit ileum

1995 ◽  
Vol 306 (1) ◽  
pp. 241-246 ◽  
Author(s):  
W Kramer ◽  
F Girbig ◽  
U Gutjahr ◽  
S Kowalewski
Keyword(s):  
Bile Acid ◽  
Transport System ◽  
Brush Border ◽  
Binding Proteins ◽  
Brush Border Membrane ◽  
High Energy ◽  
Target Size ◽  
Rabbit Ileum ◽  
Radiation Inactivation ◽  
Bile Acid Binding

The functional-unit molecular size of the Na+/bile acid cotransport system and the apparent target size of the bile-acid-binding proteins in brush-border membrane vesicles from rabbit ileum were determined by radiation inactivation with high-energy electrons. The size of the functional transporting unit for Na(+)-dependent taurocholate uptake was determined to 451 +/- 35 kDa, whereas an apparent molecular mass of 434 +/- 39 kDa was measured for the Na(+)-dependent D-glucose transport system. Proteins of 93 kDa and 14 kDa were identified as putative protein components of the ileal Na+/bile acid cotransporter in the rabbit ileum, whereas a protein of 87 kDa may be involved in passive intestinal bile acid uptake. Photoaffinity labelling with 3- and 7-azi-derivatives of taurocholate revealed a target size of 229 +/- 10 kDa for the 93 kDa protein, and 132 +/- 23 kDa for the 14 kDa protein. These findings indicate that the ileal Na+/bile acid co-transport system is in its functional state a protein complex composed of several subunits. The functional molecular sizes for Na(+)-dependent transport activity and the bile-acid-binding proteins suggest that the Na+/bile acid co-transporter from rabbit ileum is a homotetramer (AB)4 composed of four AB subunits, where A represents the integral 93 kDa and B the peripheral 14 kDa brush-border membrane protein.

Glucocorticoids upregulate taurocholate transport by ileal brush-border membrane

1997 ◽  
Vol 273 (1) ◽  
pp. G197-G203 ◽  
Author(s):  
M. J. Nowicki ◽  
B. L. Shneider ◽  
J. M. Paul ◽  
J. E. Heubi
Keyword(s):  
Steady State ◽  
Bile Acid ◽  
Western Blot ◽  
Brush Border ◽  
Blot Analysis ◽  
Western Blot Analysis ◽  
Initial Velocity ◽  
Brush Border Membrane ◽  
Membrane Vesicles ◽  
Mrna Levels

The regulation of the enterohepatic circulation of bile acids has not been fully elucidated. Substrate availability has been shown to have a regulatory role on the ileal uptake of taurocholate (TC) by a positive feedback mechanism. Other mechanisms are likely to be involved in regulating ileal bile acid uptake. The present study was designed to test the hypothesis that the ileal bile acid transporter (iBAT) is glucocorticoid sensitive and that changes in expression are mediated by changes in iBAT synthesis. Adult Sprague-Dawley rats (300–400 g) received intraperitoneal injections with either corticosterone (5 mg/ 100 g body weight) or an equivalent vehicle (control) daily for 3 days. On day 4, ileal brush-border membrane vesicles (BBMV) and hepatic basolateral membrane vesicles (BLMV) were prepared, and TC transport was performed using the rapid filtration technique. Initial velocity was measured at selected time points, and kinetics were calculated over a range of TC concentrations. Ileal RNA was isolated, and Northern analysis of steady-state iBAT mRNA levels was determined. Western blot analysis was performed to quantitate the level of the 48-kDa iBAT protein. The initial velocity of Na(+)-dependent TC uptake at 30 s by ileal BBMV was higher in treated animals (264.3 +/- 64.6 pmol/mg protein) compared with control animals (148.3 +/- 41.1 pmol/mg protein; P = 0.07). The maximal velocity of uptake (Vmax) was significantly higher in treated vs. control animals (1,091 +/- 62.7 vs. 689.1 +/- 55.0 pmol.min-1.mg protein-1, respectively; P = 0.002), whereas there was no significant difference in the Michaelis constant (Km) between the control and treated animals (43.3 +/- 7.2 vs. 35.3 +/- 8.7 microM, respectively; P = not significant). Steady-state iBAT mRNA levels were increased twofold in the treated vs. control groups. Western blot analysis showed that the abundance of the 48-kDa iBAT protein was eightfold higher in the treated animals compared with control. Kinetic analysis of hepatic Na(+)-dependent TC uptake revealed nearly identical Vmax and Km between the study and control animals. Therefore, we conclude that TC transport by ileal BBMV is upregulated by administration of glucocorticoids. The increase in BBMV transport Vmax corresponds to an increase in both iBAT transcript and protein.

Mechanism of inhibition of Na+-bile acid cotransport during chronic ileal inflammation in rabbits

1998 ◽  
Vol 275 (6) ◽  
pp. G1259-G1265 ◽  
Author(s):  
U. Sundaram ◽  
S. Wisel ◽  
S. Stengelin ◽  
W. Kramer ◽  
V. Rajendran
Keyword(s):  
Bile Acid ◽  
Amino Acid ◽  
Brush Border Membrane ◽  
Rabbit Model ◽  
Membrane Vesicles ◽  
Kinetic Studies ◽  
Transport Processes ◽  
Protein Levels ◽  
Mechanism Of Inhibition ◽  
Villus Cell

In the chronically inflamed ileum, unique mechanisms of alteration of similar transport processes suggest regulation by different immune-inflammatory mediator pathways. In a rabbit model of chronic ileitis, we previously demonstrated that Na+-glucose cotransport was inhibited by a decrease in the cotransporter numbers, whereas Na+-amino acid cotransport was inhibited by a decrease in the affinity for the amino acid. In this study, we demonstrated that Na+-bile acid cotransport was reduced in villus cells from the chronically inflamed ileum. In villus cell brush-border membrane vesicles from the chronically inflamed ileum, Na+-bile acid cotransport was reduced as well, suggesting a direct effect at the cotransporter itself. Kinetic studies demonstrated that Na+-bile acid cotransport was inhibited by both a decrease in the affinity as well as a decrease in the maximal rate of uptake of the bile acid. Analysis of steady-state mRNA and immunoreactive protein levels of the Na+-bile acid cotransporter also demonstrated some reduction during chronic ileitis. Thus, in the chronically inflamed ileum, the mechanisms of inhibition of Na+-glucose, Na+-amino acid, and Na+-bile acid cotransport are different. These data suggest that different cotransporters are uniquely altered either secondary to their intrinsic differences or by different immune-inflammatory mediators during chronic ileitis.

Intestinal transport of bile acids

1981 ◽  
Vol 241 (2) ◽  
pp. G83-G92 ◽  
Author(s):  
F. A. Wilson
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Active Transport ◽  
Brush Border ◽  
Brush Border Membrane ◽  
Water Layer ◽  
Unstirred Layer ◽  
Jejunal Mucosa ◽  
Acid Uptake ◽  
Unstirred Water Layer

The intestinal absorption of bile acids is determined by two resistances: diffusion through an unstirred water layer and penetration of the cell membrane. Passive jejunal uptake of polar bile acids is limited by the mucosal membrane, whereas the unstirred layer exerts resistance on uptake of more nonpolar species. After correction for the diffusion layer, the membrane permeability coefficients were derived to calculate the delta delta Fw leads to 1 associated with uptake of the -OH (+874 cal.mol-1), glycine (+897), and taurine (+1,498) groups. The delta delta F1 (-6,126 cal.mol-1) for the -OH group suggested that the jejunal mucosa is a relatively polar membrane. The unstirred layer is even more rate limiting for bile acid uptake from micellar solutions. Once the micelle reaches the aqueous-membrane interface, it is not absorbed intact, but rather uptake is explained in terms of monomers in the aqueous phase that are in equilibrium with the micelle. The presence of the unstirred water layer introduces artifactually high Km values for active transport. Structure-activity studies suggest that the ileal recognition site consists of a component for the steroid moiety, a positive charge, and an adjacent anionic charge. The energy for active transport arises from the Na+ gradient across the brush-border membrane that, in turn, is dependent on the activity of Na+-K+-ATPase. The Na+ stimulation of bile acid transport across the ileal brush-border membrane is due to influx coupling via a cotransport system rather than electrical coupling to satisfy overall electrical neutrality.

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