scholarly journals Review of cholesterol absorption with emphasis on dietary and biliary cholesterol.

1994 ◽  
Vol 35 (6) ◽  
pp. 943-955
Author(s):  
M D Wilson ◽  
L L Rudel
2006 ◽  
Vol 290 (2) ◽  
pp. G269-G276 ◽  
Author(s):  
Li-Ping Duan ◽  
Helen H. Wang ◽  
Akira Ohashi ◽  
David Q.-H. Wang

Recent studies have indicated that intestinal cholesterol absorption is a multistep process, which is regulated by multiple genes at the enterocyte level. However, the molecular mechanisms whereby there are gender differences in intestinal cholesterol absorption efficiency and the efficiency of cholesterol absorption increases with age have not yet been fully understood. To explore whether aging increases cholesterol absorption via intestinal sterol transporters, we studied the higher cholesterol-absorbing C57L/J vs. the lower cholesterol-absorbing AKR/J mice at 8 (young adult), 36 (older adult), and 50 (aged) wk of age. To test the hypothesis that estrogen receptor (ER )α plays an important regulatory role in cholesterol absorption, we investigated the gonadectomized mice of both genders treated with 17β-estradiol-releasing pellets at 0, 3, or 6 μg/day and antiestrogenic ICI 182,780 at 125 μg/day. We found that hepatic outputs of biliary cholesterol were significantly increased with age and in response to high levels of estrogen. Aging significantly enhances cholesterol absorption by suppressing expression of the jejunal and ileal sterol efflux transporters [ATP-binding cassette ( Abc) g5 and Abcg8] and upregulating expression of the putative duodenal and jejunal sterol influx transporter Npc1l1. Estrogen significantly augmented cholesterol absorption mostly due to an upregulated expression of intestinal Npc1l1, Abcg5, and Abcg8 via the intestinal ERα pathway, which can be fully abolished by the antagonist. We conclude that ERα activated by estrogen and aging enhances cholesterol absorption by increasing biliary lipid output and mediating intestinal sterol transporters favoring influx of intraluminal cholesterol molecules across the apical membrane of the enterocyte.


1998 ◽  
Vol 95 (17) ◽  
pp. 10194-10199 ◽  
Author(s):  
E. Sehayek ◽  
J. G. Ono ◽  
S. Shefer ◽  
L. B. Nguyen ◽  
N. Wang ◽  
...  

2007 ◽  
Vol 39 (7) ◽  
pp. 646-653
Author(s):  
F. Liguori ◽  
N. Domingo ◽  
G. Tebala ◽  
C. Ripani ◽  
R. De Marco ◽  
...  

1999 ◽  
Vol 276 (3) ◽  
pp. G751-G760 ◽  
Author(s):  
David Q.-H. Wang ◽  
Frank Lammert ◽  
David E. Cohen ◽  
Beverly Paigen ◽  
Martin C. Carey

Cholic acid is a critical component of the lithogenic diet in mice. To determine its pathogenetic roles, we fed chow or 1% cholesterol with or without 0.5% cholic acid to C57L/J male mice, which because of lith genes have 100% gallstone prevalence rates. After 1 yr on the diets, we measured bile flow, biliary lipid secretion rates, hepatic cholesterol and bile salt synthesis, and intestinal cholesterol absorption. After hepatic conjugation with taurine, cholate replaced most tauro-β-muricholate in bile. Dietary cholic acid plus cholesterol increased bile flow and biliary lipid secretion rates and reduced cholesterol 7α-hydroxylase activity significantly mostly via deoxycholic acid, cholate’s bacterial 7α-dehydroxylation product but did not downregulate cholesterol biosynthesis. Intestinal cholesterol absorption doubled, and biliary cholesterol crystallized as phase boundaries shifted. Feeding mice 1% cholesterol alone produced no lithogenic or homeostatic effects. We conclude that in mice cholic acid promotes biliary cholesterol hypersecretion and cholelithogenesis by enhancing intestinal absorption, hepatic bioavailability, and phase separation of cholesterol in bile.


2008 ◽  
Vol 295 (4) ◽  
pp. G813-G822 ◽  
Author(s):  
Mark A. Valasek ◽  
Joyce J. Repa ◽  
Gang Quan ◽  
John M. Dietschy ◽  
Stephen D. Turley

Niemann-Pick C1-like 1 (NPC1L1) facilitates the uptake of sterols into the enterocyte and is the target of the novel cholesterol absorption inhibitor, ezetimibe. These studies used the Golden Syrian hamster as a model to delineate the changes in the relative mRNA expression of NPC1L1 and other proteins that regulate sterol homeostasis in the enterocyte during and following cessation of ezetimibe treatment and also to address the clinically important question of whether the marked inhibition of cholesterol absorption alters biliary lipid composition. In hamsters fed a low-cholesterol, low-fat basal diet, the abundance of mRNA for NPC1L1 in the small intestine far exceeded that in other regions of the gastrointestinal tract, liver, and gallbladder. In the first study, female hamsters were fed the basal diet containing ezetimibe at doses up to 2.0 mg·day−1·kg body wt−1. At this dose, cholesterol absorption fell by 82%, fecal neutral sterol excretion increased by 5.3-fold, and hepatic and intestinal cholesterol synthesis increased more than twofold, but there were no significant changes in either fecal bile acid excretion or biliary lipid composition. The ezetimibe-induced changes in intestinal cholesterol handling were reversed when treatment was withdrawn. In a second study, male hamsters were given a diet enriched in cholesterol and safflower oil without or with ezetimibe. The lipid-rich diet raised the absolute and relative cholesterol levels in bile more than fourfold. This increase was largely prevented by ezetimibe. These data are consistent with the recent finding that ezetimibe treatment significantly reduced biliary cholesterol saturation in patients with gallstones.


Lipids ◽  
1979 ◽  
Vol 14 (5) ◽  
pp. 441-446 ◽  
Author(s):  
C. Lutton ◽  
E. Brot-Laroche

2001 ◽  
Vol 33 ◽  
pp. A3
Author(s):  
S.Ginanni Corradini ◽  
F. Liguori ◽  
N. Domingo ◽  
P. Lechene de la Porte ◽  
A. Eramo ◽  
...  

1991 ◽  
Vol 66 (3) ◽  
pp. 479-492 ◽  
Author(s):  
J. Khallou ◽  
M. Riottot ◽  
M. Parquet ◽  
C. Verneau ◽  
C. Lutton

By using the isotopic equilibrium method in the young male Syrian hamster, the rates of cholesterol turnover processes, i.e. dietary cholesterol absorption, cholesterol synthesis, cholesterol excretion in the faeces and urine and cholesterol transformation into bile acids, were determined in the hamster receiving a control (C) or a lithogenic diet (L) for 7 weeks. At the end of this period the gall bladder of all animals in group L contained cholesterol gallstones. The coefficient of dietary cholesterol absorption was reduced by 26 %, cholesterol synthesis and cholesterol faecal excretion were twofold higher in group L than in group C. Bile acid content in the small intestine was diminished in group L, but bile acid composition was similar in the two groups. The increase in cholesterogenesis in lithiasic animals essentially took place in the liver. Bile acid biosynthesis did not significantly differ in the two groups, but represented only 35 % of total cholesterol input (dietary absorption + internal secretion) in group L ν. 52% in group C. Thus, in the lithiasic hamster, hepatic synthesis of cholesterol and bile acids are not coupled. The molar percentage of cholesterol in bile was twofold higher in group L than in group C but those of bile acids and of phospholipids were not modified. In the lithiasic hamster the specific activity of biliary cholesterol was similar to that in plasma and liver. Consequently, biliary cholesterol does not derive directly from cholesterol newly synthesized in the liver but from hepatic cholesterol rapidly exchangeable with plasma cholesterol.


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