Analysis of the effect of intestinal resection on rat ileal bile Acid transporter expression and on bile Acid and cholesterol homeostasis.
Ileal reclamation of bile salts is mediated in large part by an apical sodium-dependent bile acid transporter (ASBT) located in the terminal ileum. The following studies were performed to elucidate the adaptive response of ASBT to intestinal resection. Two separate series of intestinal resections were performed: 1) limited (25%) ileal and 2) massive (70%) intestinal resection. The boundaries of the resections were varied to examine differences in compensation when variable amounts of endogenous transporter activity were resected. Previously demonstrated supraphysiologic expression of ASBT, which was seen after proximal ileal resection, led to a contraction in the bile acid pool size and a paradoxical reduction in bile acid (cholesterol 7alpha-hydroxylase and sterol 27-hydroxylase) and cholesterol (hydroxymethylglutaryl coenzyme A reductase) biosynthetic enzyme activities. Massive intestinal resection resulted in ileal hypertrophy and an apparently maladaptive specific down-regulation in ASBT protein expression. In this model bile acid pool size correlated with the amount of residual ASBT-expressing terminal ileum. Cholesterol and bile acid biosynthetic enzyme activities were inversely related to bile acid pool size. Adaptive changes in ASBT expression and alterations in bile acid and cholesterol homeostasis are dependent on the type and location of intestinal resection.
Al-Ansari
Namir
N
Mount Sinai School of Medicine, New York, New York 10029, USA.
Xu
Guorong
G
Kollman-Bauerly
Katie
K
Coppola
Chris
C
Shefer
Sarah
S
Ujhazy
Peter
P
Ortiz
Daniel
D
Ma
Lin
L
Yang
Steven
S
Tsai
Richard
R
Salen
Gerald
G
Vanderhoof
Jon
J
Shneider
Benjamin L
BL
D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism*; D002352:Carrier Proteins / Q000032:analysis / Q000096:biosynthesis*; D053493:Cholestanetriol 26-Monooxygenase; D002784:Cholesterol / Q000378:metabolism*; D002790:Cholesterol 7-alpha-Hydroxylase / Q000378:metabolism; D006706:Homeostasis / Q000502:physiology; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D007082:Ileum / Q000378:metabolism* / Q000601:surgery*; D008297:Male; D008871:Microvilli / Q000201:enzymology; D023421:Models, Animal; D029363:Organic Anion Transporters, Sodium-Dependent; D051381:Rats; D017207:Rats, Sprague-Dawley; D012778:Short Bowel Syndrome / Q000378:metabolism / Q000601:surgery; D013250:Steroid Hydroxylases / Q000378:metabolism; D027981:Symporters
D001647:Bile Acids and Salts; D002352:Carrier Proteins; D029363:Organic Anion Transporters, Sodium-Dependent; D027981:Symporters; C071908:sodium-bile acid cotransporter; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases; D013250:Steroid Hydroxylases; D002790:Cholesterol 7-alpha-Hydroxylase; D053493:Cholestanetriol 26-Monooxygenase