The Experts below are selected from a list of 234 Experts worldwide ranked by ideXlab platform
Albert K Groen - One of the best experts on this subject based on the ideXlab platform.
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Hepatic ABCG5/G8 overexpression substantially increases biliary choleSterol secretion but does not impact in vivo macrophage-to-feces RCT.
Atherosclerosis, 2015Co-Authors: Arne Dikkers, Albert K Groen, Jan Freark De Boer, Uwe J. F. TietgeAbstract:Abstract Background and aims Biliary choleSterol secretion is important for reverse choleSterol transport (RCT). ABCG5/G8 contribute most choleSterol mass secretion into bile. We investigated the impact of hepatic ABCG5/G8 on choleSterol metabolism and RCT. Methods Biliary and fecal Sterol Excretion (FSE) as well as RCT were determined using wild-type controls, Abcg8 knockout mice, Abcg8 knockouts with adenovirus-mediated hepatocyte-specific Abcg8 reinstitution and hepatic Abcg5/g8 overexpression in wild-types. Results In Abcg8 knockouts, biliary choleSterol secretion was decreased by 75% (p Conclusions ABCG5/G8 mediate mass biliary choleSterol secretion but not from a RCT-relevant pool. Intervention strategies aiming at increasing hepatic Abcg5/g8 expression for enhancing RCT are not likely to be successful.
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A reappraisal of the mechanism by which plant Sterols promote neutral Sterol loss in mice.
PLOS ONE, 2011Co-Authors: Gemma Brufau, Elke A Trautwein, Folkert Kuipers, Albert K GroenAbstract:Dietary plant Sterols (PS) reduce serum total and LDL-choleSterol in hyperlipidemic animal models and in humans. This hypocholeSterolemic effect is generally ascribed to inhibition of choleSterol absorption. However, whether this effect fully explains the reported strong induction of neutral Sterol Excretion upon plant Sterol feeding is not known. Recent data demonstrate that the intestine directly mediates plasma choleSterol Excretion into feces, i.e., without involvement of the hepato-biliary route. Objective: Aim of this study was to determine whether stimulation of fecal neutral Sterol loss during PS feeding is (partly) explained by increased intestinal choleSterol Excretion and to assess the role of the choleSterol transporter Abcg5/Abcg8 herein. Methods and Results: Wild-type mice were fed a control diet or diets enriched with increasing amounts of PS (1%, 2%, 4% or 8%, wt/wt) for two weeks. In addition, Abcg5(-/-) mice were fed either control or 8% PS diet. PS feeding resulted in a dose-dependent decrease of fractional choleSterol absorption (similar to 2-7-fold reduction) in wild-type mice and similar to 80% reduction in Abcg5(-/-) mice. Furthermore, PS feeding led to a strong, dose-independent induction of neutral Sterol Excretion (3.4-fold in wild-types and 2.7-fold in Abcg5(-/-) mice) without changes in biliary choleSterol secretion. It was calculated that PS feeding stimulated intestinal choleSterol Excretion by similar to 500% in wild-type mice and by similar to 250% in Abcg5(-/-). Conclusions: Our data indicate that in mice the choleSterol-lowering effects of PS are to a large extent attributable to stimulation of intestinal, non-bile derived, choleSterol Excretion. The Abcg5/Abcg8 heterodimer is involved in facilitating this PS-induced flux of choleSterol.
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ezetimibe stimulates faecal neutral Sterol Excretion depending on abcg8 function in mice
FEBS Letters, 2010Co-Authors: Lily Jakulj, Frans Stellaard, John J P Kastelein, Maud N Vissers, Cindy P A A Van Roomen, Jelske N Van Der Veen, Carlos L J Vrins, Cindy Kunne, Albert K GroenAbstract:Ezetimibe stimulates faecal neutral Sterol (FNS) Excretion in mice, which cannot be explained by choleSterol absorption inhibition alone. We investigated whether these effects are mediated via the Sterol exporter ATP binding cassette transporter G8 (abcg8). Ezetimibe increased FNS Excretion 2.7-fold in WT mice and 1.5-fold in abcg8−/− mice, without affecting biliary choleSterol secretion. Daily FNS Excretion exceeded the sum of dietary choleSterol intake and biliary secretion by about 60%. Ezetimibe enhanced this ‘extra’ FNS Excretion by 3.5-fold and 1.5-fold in wildtype (WT) and abcg8−/− mice, respectively. Ezetimibe stimulates fecal Sterol Excretion of non-biliary and non-dietary origin, probably through stimulation of trans-intestinal choleSterol Excretion. We show that this effect depends on intact abcg8 function.
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Transintestinal choleSterol efflux.
Current Opinion in Lipidology, 2010Co-Authors: Astrid E Van Der Velde, Gemma Brufau, Albert K GroenAbstract:Purpose of review Regulation of choleSterol homeostasis is a complex interplay of a multitude of metabolic pathways situated in different organs. The liver plays a central role and has received most attention of the research community. In this review, we discuss recent progress in the understanding of the emerging role of the intestine in choleSterol transport. Recent findings In recent years, insight in the transport systems that mediate intestinal choleSterol Excretion has deepened considerably. Evidence is emerging that the proximal part of the small intestine is able to secrete choleSterol actively, a pathway called transintestinal choleSterol efflux (TICE). In mice, TICE accounts for up to 70% of fecal neutral Sterol Excretion. Summary The small intestine plays a significant role in the regulation of body choleSterol homeostasis. Active processes control both absorption and Excretion of the Sterol and the pathways involved are being elucidated. TICE might provide an attractive target for therapy aiming at reduction of atherosclerosis.
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reduced fecal Sterol Excretion in subjects with familial hypoalphalipoproteinemia
Atherosclerosis, 2009Co-Authors: Karim El Harchaoui, Remco Franssen, Kees G Hovingh, Radjesh J Bisoendial, Frans Stellaard, Folkert Kuipers, John J P Kastelein, Jan Albert Kuivenhoven, Erik S G Stroes, Albert K GroenAbstract:BACKGROUND: Fecal bile acid and neutral Sterol Excretion are the obligate endpoints of the reverse choleSterol transport pathway (RCT). In studies in mice, no evidence was found for a relation between HDL-choleSterol (HDL-c) levels and fecal Sterol Excretion. In this study, we have evaluated this relationship in patients with isolated low HDL-c versus controls. RESULTS: Fecal Sterol Excretion was studied in 12 subjects with familial hypoalphalipoproteinemia (FHA) and 11 healthy controls. Compared to the controls (8.9+/-6.3mg/kg/day), neutral Sterol Excretion was significantly lower in the FHA group (4.0+/-2.4mg/kg/day). Fecal bile acid Excretion showed a similar pattern. Across the groups, a strong positive correlation between HDL-c and fecal neutral Sterol Excretion was found (r=0.53; p=0.01). CONCLUSIONS: Isolated low HDL-c levels in humans are associated with reduced fecal Sterol Excretion suggesting that in humans HDL regulates the final step in the RCT pathway at low HDL-c levels.
Timothy P Carr - One of the best experts on this subject based on the ideXlab platform.
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Hypolipidemic Effect of a Blue-Green Alga (Nostoc commune) Is Attributed to Its Nonlipid Fraction by Decreasing Intestinal CholeSterol Absorption in C57BL/6J Mice.
Journal of Medicinal Food, 2015Co-Authors: Chai Siah Ku, Timothy P Carr, Tho X. Pham, Yue Yang, Curtis L. Weller, Young-ki ParkAbstract:Abstract We previously demonstrated that Nostoc commune var. sphaeroids Kutzing (NO), a blue-green alga (BGA), exerts a hypolipidemic effect in vivo and its lipid extract regulates the expression of genes involved in choleSterol and lipid metabolism in vitro. The objective of this study was to investigate whether the hypolipidemic effect of NO is attributed to an algal lipid or a delipidated fraction in vivo compared with Spirulina platensis (SP). Male C57BL/6J mice were fed an AIN-93M diet containing 2.5% or 5% of BGA (w/w) or a lipid extract equivalent to 5% of BGA for 4 weeks to measure plasma and liver lipids, hepatic gene expression, intestinal choleSterol absorption, and fecal Sterol Excretion. Plasma total choleSterol (TC) was significantly lower in 2.5% and 5% NO-fed groups, while plasma triglyceride (TG) levels were decreased in the 5% NO group compared with controls. However, neither NO organic extract (NOE) nor SP-fed groups altered plasma lipids. Hepatic mRNA levels of Sterol regulatory elemen...
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phytoSterol stearate esters elicit similar responses on plasma lipids and choleSterol absorption but different responses on fecal neutral Sterol Excretion and hepatic free choleSterol in male syrian hamsters
Nutrition Research, 2011Co-Authors: Jiliang Hang, Patrick H Dussault, Timothy P CarrAbstract:Abstract The dietary impact of specific phytoSterols incorporated into phytoSterol fatty acid esters has not been elucidated. Therefore, we tested the hypothesis that phytoSterol esters containing different Sterol moieties (sitoSterol, sitostanol, or stigmaSterol) but the same fatty acid moiety (stearic acid) produce different effects on choleSterol metabolism. Male Syrian hamsters were fed sitoSterol, sitostanol, and stigmaSterol stearate esters (25 g/kg diet) in an atherogenic diet containing choleSterol (1.2 g/kg) and coconut oil (80 g/kg). The phytoSterol stearates produced no decrease in choleSterol absorption or plasma non–high-density lipoprotein choleSterol despite a reduction in liver free choleSterol in hamsters fed both sitoSterol and sitostanol stearate diets. In addition, sitoSterol stearate significantly increased fecal esterified and total neutral Sterol Excretion. StigmaSterol stearate did not differ from control in neutral Sterol Excretion, plasma lipids, or hepatic lipid concentration. SitoSterol stearate demonstrated the highest level of net intestinal hydrolysis, whereas sitostanol and stigmaSterol stearate equivalently demonstrated the lowest. The choleSterol-lowering effect in liver—but not plasma—and the limited presence of fecal free Sterols indicate that intact (unhydrolyzed) phytoSterol stearates may impact choleSterol metabolism by mechanisms unrelated to the role of free phytoSterols. The consumption of phytoSterol esters at 2.5% of the diet elicited only modest impacts on choleSterol metabolism, although sitoSterol stearate had a slightly greater therapeutic impact by lowering liver free choleSterol and increasing esterified and total neutral Sterol fecal Excretion, possibly due to a greater level of intestinal hydrolysis.
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HypocholeSterolemic effect of Nostoc commune var. sphaeroides Kützing, an edible blue-green alga
European Journal of Nutrition, 2009Co-Authors: Heather E. Rasmussen, Kara R. Blobaum, Elliot D. Jesch, Chai Siah Ku, Young-ki Park, Fan Lu, Timothy P CarrAbstract:Background Intake of an edible blue-green alga Nostoc commune var. sphaeroides Kützing ( N. Commune ) has been shown to lower plasma total choleSterol concentration, but the mechanisms behind the hypocholeSterolemic effect have not been elucidated. Aim of the study To elucidate the mechanisms underlying the choleSterol-lowering effect of N. commune in mice. Methods Male C57BL/6J mice were fed the AIN-93 M diet supplemented with 0 or 5% (wt/wt) dried N. Commune for 4 weeks. Lipid levels in the plasma and liver, intestinal choleSterol absorption and fecal Sterol Excretion were measured. Expression of hepatic and intestinal genes involved in choleSterol metabolism was evaluated by quantitative realtime PCR. Results N. commune supplementation significantly reduced total plasma choleSterol and triglyceride concentrations by ~ 20% compared to controls. Intestinal choleSterol absorption was significantly decreased, while fecal neutral Sterol output was significantly increased in N. commune -fed mice. mRNA levels of the choleSterol transporters such as Niemann Pick C1 Like 1, scavenger receptor class B type 1, ATP-binding cassette transporters G5 and A1 in small intestine were not significantly different between two groups. Hepatic lipid contents including total choleSterol, triglyceride and free choleSterol in N. commune- fed mice were not significantly altered. However, the expression of choleSterol modulating genes including Sterol regulatory element binding protein-2 and 3-hydroxy-3-methylglutaryl coenzyme A reductase were significantly increased in mice fed N. commune . Conclusions N. commune supplementation exerted a hypocholeSterolemic effect in mice, largely in part, by reducing intestinal choleSterol absorption and promoting fecal neutral Sterol Excretion.
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Reduction in CholeSterol Absorption Is Enhanced by Stearate-Enriched Plant Sterol Esters in Hamsters
Journal of Nutrition, 2006Co-Authors: Heather E. Rasmussen, Patrick H Dussault, David M. Guderian, Curtis A. Wray, Vicki Schlegel, Timothy P CarrAbstract:: Consumption of plant Sterol esters reduces plasma LDL choleSterol concentration by inhibiting intestinal choleSterol absorption. Commercially available plant Sterol esters are prepared by esterifying free Sterols to fatty acids from edible plant oils such as canola, soybean, and sunflower. To determine the influence of the fatty acid moiety on choleSterol metabolism, plant Sterol esters were made with fatty acids from soybean oil (SO), beef tallow (BT), or purified stearic acid (SA) and fed to male hamsters for 4 wk. A control group fed no plant Sterol esters was also included. Hamsters fed BT and SA had significantly lower choleSterol absorption and decreased concentrations of plasma non-HDL choleSterol and liver esterified choleSterol, and significantly greater fecal Sterol Excretion than SO and control hamsters. CholeSterol absorption was lowest in hamsters fed SA (7.5%), whereas it was 72.9% in control hamsters. CholeSterol absorption was correlated with fecal Sterol Excretion (r = -0.72, P < 0.001), liver choleSterol concentration (r = 0.88, P < 0.001), and plasma non-HDL choleSterol concentration (r = 0.85, P < 0.001). A multiple regression model that included each Sterol ester type vs. choleSterol absorption indicated that intake of steryl stearate was the only dietary component that contributed significantly to the model (R2 = -0.75, P < 0.001). Therefore, our results demonstrate that BT and SA are more effective than SO in reducing choleSterol absorption, liver choleSterol, and plasma non-HDL choleSterol concentration, suggesting that cardioprotective benefits can be achieved by consuming stearate-enriched plant Sterol esters.
Sonya Vanpatten - One of the best experts on this subject based on the ideXlab platform.
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Hepatic choleSterol and bile acid metabolism and intestinal choleSterol absorption in scavenger receptor class B type I (SR-BI)-deficient mice
Gastroenterology, 2001Co-Authors: Pablo Mardones, Juan Francisco Miquel, Veronica Quinones, Ludwig Amigo, Mauricio Moreno, Margrit Schwarz, Helena E Miettinen, Bernardo L Trigatti, Monty Krieger, Sonya VanpattenAbstract:The scavenger receptor class B type I (SR-BI), which is expressed in the liver and intestine, plays a critical role in choleSterol metabolism in rodents. While hepatic SR-BI expression controls high density lipoprotein (HDL) choles- terol metabolism, intestinal SR-BI has been proposed to facilitate choleSterol absorption. To evaluate further the rel- evance of SR-BI in the enterohepatic circulation of choles- terol and bile salts, we studied biliary lipid secretion, he- patic Sterol content and synthesis, bile acid metabolism, fecal neutral Sterol Excretion, and intestinal choleSterol ab- sorption in SR-BI knockout mice. SR-BI deficiency selec- tively impaired biliary choleSterol secretion, without con- comitant changes in either biliary bile acid or phospholipid secretion. Hepatic total and unesterified choleSterol con- tents were slightly increased in SR-BI-deficient mice, while Sterol synthesis was not significantly changed. Bile acid pool size and composition, as well as fecal bile acid Excretion, were not altered in SR-BI knockout mice. Intestinal choles- terol absorption was somewhat increased and fecal Sterol Excretion was slightly decreased in SR-BI knockout mice rel- ative to controls. These findings establish the critical role of hepatic SR-BI expression in selectively controlling the utilization of HDL choleSterol for biliary secretion. In con- trast, SR-BI expression is not essential for intestinal choles-
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hepatic choleSterol and bile acid metabolism and intestinal choleSterol absorption in scavenger receptor class b type i deficient mice
Journal of Lipid Research, 2001Co-Authors: Pablo Mardones, Juan Francisco Miquel, Veronica Quinones, Ludwig Amigo, Mauricio Moreno, Margrit Schwarz, Helena E Miettinen, Bernardo L Trigatti, Monty Krieger, Sonya VanpattenAbstract:: The scavenger receptor class B type I (SR-BI), which is expressed in the liver and intestine, plays a critical role in choleSterol metabolism in rodents. While hepatic SR-BI expression controls high density lipoprotein (HDL) choleSterol metabolism, intestinal SR-BI has been proposed to facilitate choleSterol absorption. To evaluate further the relevance of SR-BI in the enterohepatic circulation of choleSterol and bile salts, we studied biliary lipid secretion, hepatic Sterol content and synthesis, bile acid metabolism, fecal neutral Sterol Excretion, and intestinal choleSterol absorption in SR-BI knockout mice. SR-BI deficiency selectively impaired biliary choleSterol secretion, without concomitant changes in either biliary bile acid or phospholipid secretion. Hepatic total and unesterified choleSterol contents were slightly increased in SR-BI-deficient mice, while Sterol synthesis was not significantly changed. Bile acid pool size and composition, as well as fecal bile acid Excretion, were not altered in SR-BI knockout mice. Intestinal choleSterol absorption was somewhat increased and fecal Sterol Excretion was slightly decreased in SR-BI knockout mice relative to controls. These findings establish the critical role of hepatic SR-BI expression in selectively controlling the utilization of HDL choleSterol for biliary secretion. In contrast, SR-BI expression is not essential for intestinal choleSterol absorption.
H Andersson - One of the best experts on this subject based on the ideXlab platform.
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will recommended changes in fat and fibre intake affect choleSterol absorption and Sterol Excretion an ileostomy study
European Journal of Clinical Nutrition, 2000Co-Authors: Lars Ellegard, Ingvar Bosaeus, H AnderssonAbstract:Objective: To study choleSterol absorption and Excretion in ileostomy subjects with different intakes of saturated fat and dietary fibre. Design: Short-term experimental study, with four controlled diets in repeated measurements. Setting: Out-patients at metabolic-ward kitchen. Subjects: Nine healthy volunteers with conventional ileostomy after colectomy because of ulcerative colitis. Interventions: Four diet periods, each of 3 days duration: high saturated fat and low dietary fibre (STAND); reduced saturated fat (RESAT); high saturated fat and high fibre (FATFIB); and reduced saturated fat and high fibre (RESATFIB). Main outcome measures: Absorption of choleSterol, and ileal Excretion of choleSterol, bile acids, fat and energy. Differences between diets evaluated with Friedman’s two-way analysis of variance by rank sum with Bonferroni adjustment, and post hoc differences assessed by rank sum comparison. Results: RESAT and RESATFIB reduced fractional choleSterol absorption by 7% and 10%; RESATFIB and FATFIB increased net choleSterol Excretion by 46% and 54% respectively. Further, RESATFIB increased net Sterol Excretion by 18%, all compared to STAND (P<0.05 for all). All three intervention diets contained more phytoSterols than STAND (P<0.05), and the phytoSterol content was inversely correlated to fractional choleSterol absorption (r=−0.77, P<0.01). Conclusions: Current nutrition recommendations to reduce saturated fat and increase dietary fibre affect Sterol Excretion additively. The effect on choleSterol absorption might be partly explained by the content of dietary plant Sterols. Sponsorship: Supported by grants from the Gothenburg Medical Society, grant numbers 94/086 and 99/082, and by the University of Gothenburg. European Journal of Clinical Nutrition (2000) 54, 306–313
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Will recommended changes in fat and fibre intake affect choleSterol absorption and Sterol Excretion? An ileostomy study
European Journal of Clinical Nutrition, 2000Co-Authors: Lars Ellegard, I Bosaeus, H AnderssonAbstract:Objective: To study choleSterol absorption and Excretion in ileostomy subjects with different intakes of saturated fat and dietary fibre. Design: Short-term experimental study, with four controlled diets in repeated measurements. Setting: Out-patients at metabolic-ward kitchen. Subjects: Nine healthy volunteers with conventional ileostomy after colectomy because of ulcerative colitis. Interventions: Four diet periods, each of 3 days duration: high saturated fat and low dietary fibre (STAND); reduced saturated fat (RESAT); high saturated fat and high fibre (FATFIB); and reduced saturated fat and high fibre (RESATFIB). Main outcome measures: Absorption of choleSterol, and ileal Excretion of choleSterol, bile acids, fat and energy. Differences between diets evaluated with Friedman’s two-way analysis of variance by rank sum with Bonferroni adjustment, and post hoc differences assessed by rank sum comparison. Results: RESAT and RESATFIB reduced fractional choleSterol absorption by 7% and 10%; RESATFIB and FATFIB increased net choleSterol Excretion by 46% and 54% respectively. Further, RESATFIB increased net Sterol Excretion by 18%, all compared to STAND ( P
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alginate small bowel Sterol Excretion and absorption of nutrients in ileostomy subjects
The American Journal of Clinical Nutrition, 1994Co-Authors: Annsofie Sandberg, Ingvar Bosaeus, H Andersson, Nilsgunnar Carlsson, Kristina Hasselblad, Magnus HarrodAbstract:The effect of alginate on ileostomy Excretion of stenols and nutrients was investigated in six ileostomy subjects fed a constant low-fiber diet with on without supplementation with 7.5 g sodium alginate. A mean of 95% of uronic acids de- rived from the sodium alginate was recovered in the ileostomy contents. Supplementation with alginate increased fat Excretion by 140% and decreased bile acids Excretion by 12%. Sodium and potassium Excretion were significantly increased whereas starch and nitrogen Excretion were unchanged. Five of six subjects showed a decreased apparent absorption of iron and manganese with alginate, which, however, was not statistically significant. Absorption of phosphorus, calcium, magnesium, and zinc were unchanged. Almost no digestion of sodium alginate occurs in the stomach and small intestine. The increased fatty acids Excretion may be explained by the binding or trapping of fatty acids in the gel matrix formed by alginate, which may also cause a reduced bileflow. AmJC/inNutr l994;60:75l-6.
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the ileostomy model for the study of carbohydrate digestion and carbohydrate effects on Sterol Excretion in man
European Journal of Clinical Nutrition, 1992Co-Authors: H AnderssonAbstract:: The ileostomy model offers a method for direct, accurate and quantitative determination of small bowel Excretion, provided the bacteriological degradation of the effluent can be minimized. The intraindividual variation is small, and rapid changes in Excretion pattern due to dietary manipulations can be measured. Such ileostomy investigations have been important for developing the resistant starch and dietary fibre concepts. Using this method, various mechanisms for effects of dietary fibre on plasma lipids can be elucidated, e.g. binding of choleSterol, bile acids and/or lipids. Another application is to study the capacity of phytic acid and its degradation products to bind minerals in the small bowel.
Pablo Mardones - One of the best experts on this subject based on the ideXlab platform.
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Hepatic choleSterol and bile acid metabolism and intestinal choleSterol absorption in scavenger receptor class B type I (SR-BI)-deficient mice
Gastroenterology, 2001Co-Authors: Pablo Mardones, Juan Francisco Miquel, Veronica Quinones, Ludwig Amigo, Mauricio Moreno, Margrit Schwarz, Helena E Miettinen, Bernardo L Trigatti, Monty Krieger, Sonya VanpattenAbstract:The scavenger receptor class B type I (SR-BI), which is expressed in the liver and intestine, plays a critical role in choleSterol metabolism in rodents. While hepatic SR-BI expression controls high density lipoprotein (HDL) choles- terol metabolism, intestinal SR-BI has been proposed to facilitate choleSterol absorption. To evaluate further the rel- evance of SR-BI in the enterohepatic circulation of choles- terol and bile salts, we studied biliary lipid secretion, he- patic Sterol content and synthesis, bile acid metabolism, fecal neutral Sterol Excretion, and intestinal choleSterol ab- sorption in SR-BI knockout mice. SR-BI deficiency selec- tively impaired biliary choleSterol secretion, without con- comitant changes in either biliary bile acid or phospholipid secretion. Hepatic total and unesterified choleSterol con- tents were slightly increased in SR-BI-deficient mice, while Sterol synthesis was not significantly changed. Bile acid pool size and composition, as well as fecal bile acid Excretion, were not altered in SR-BI knockout mice. Intestinal choles- terol absorption was somewhat increased and fecal Sterol Excretion was slightly decreased in SR-BI knockout mice rel- ative to controls. These findings establish the critical role of hepatic SR-BI expression in selectively controlling the utilization of HDL choleSterol for biliary secretion. In con- trast, SR-BI expression is not essential for intestinal choles-
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hepatic choleSterol and bile acid metabolism and intestinal choleSterol absorption in scavenger receptor class b type i deficient mice
Journal of Lipid Research, 2001Co-Authors: Pablo Mardones, Juan Francisco Miquel, Veronica Quinones, Ludwig Amigo, Mauricio Moreno, Margrit Schwarz, Helena E Miettinen, Bernardo L Trigatti, Monty Krieger, Sonya VanpattenAbstract:: The scavenger receptor class B type I (SR-BI), which is expressed in the liver and intestine, plays a critical role in choleSterol metabolism in rodents. While hepatic SR-BI expression controls high density lipoprotein (HDL) choleSterol metabolism, intestinal SR-BI has been proposed to facilitate choleSterol absorption. To evaluate further the relevance of SR-BI in the enterohepatic circulation of choleSterol and bile salts, we studied biliary lipid secretion, hepatic Sterol content and synthesis, bile acid metabolism, fecal neutral Sterol Excretion, and intestinal choleSterol absorption in SR-BI knockout mice. SR-BI deficiency selectively impaired biliary choleSterol secretion, without concomitant changes in either biliary bile acid or phospholipid secretion. Hepatic total and unesterified choleSterol contents were slightly increased in SR-BI-deficient mice, while Sterol synthesis was not significantly changed. Bile acid pool size and composition, as well as fecal bile acid Excretion, were not altered in SR-BI knockout mice. Intestinal choleSterol absorption was somewhat increased and fecal Sterol Excretion was slightly decreased in SR-BI knockout mice relative to controls. These findings establish the critical role of hepatic SR-BI expression in selectively controlling the utilization of HDL choleSterol for biliary secretion. In contrast, SR-BI expression is not essential for intestinal choleSterol absorption.