Mechanisms for cholesterol homeostasis in rat jejunal mucosa: effects of cholesterol, sitosterol, and lovastatin

The effects of feeding cholesterol, sitosterol, and lovastatin on cholesterol absorption, biosynthesis, esterification, and LDL receptor function were examined in the rat jejunal mucosa. Cholesterol absorption was measured by the dual-isotope plasma ratio method; the rate-limiting enzyme of choleste...

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Main Authors: Lien B. Nguyen, Sarah Shefer, Gerald Salen, G.S. Tint, Frank Ruiz, John Bullock
Format: Article
Language:English
Published: Elsevier 2001-02-01
Series:Journal of Lipid Research
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S0022227520316795
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spelling doaj-fe2ec2f5c03d4b7fbbb09e3bb8d73a772021-04-27T04:40:35ZengElsevierJournal of Lipid Research0022-22752001-02-01422195200Mechanisms for cholesterol homeostasis in rat jejunal mucosa: effects of cholesterol, sitosterol, and lovastatinLien B. Nguyen0Sarah Shefer1Gerald Salen2G.S. Tint3Frank Ruiz4John Bullock5To whom correspondence should be addressed.; Department of Medicine/Division of Gastroenterology and Liver Center, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, NJ 07103Department of Medicine/Division of Gastroenterology and Liver Center, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, NJ 07103Department of Medicine/Division of Gastroenterology and Liver Center, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, NJ 07103; New Jersey Veterans Healthcare System, East Orange, NJ 07019Department of Medicine/Division of Gastroenterology and Liver Center, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, NJ 07103; New Jersey Veterans Healthcare System, East Orange, NJ 07019Department of Medicine/Division of Gastroenterology and Liver Center, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, NJ 07103Department of Pharmacology and Physiology, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, NJ 07103The effects of feeding cholesterol, sitosterol, and lovastatin on cholesterol absorption, biosynthesis, esterification, and LDL receptor function were examined in the rat jejunal mucosa. Cholesterol absorption was measured by the dual-isotope plasma ratio method; the rate-limiting enzyme of cholesterol biosynthesis, 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, was measured as total and expressed enzyme activities (in the absence and presence of a phosphatase inhibitor, NaF, respectively); mucosal total and esterified cholesterol concentrations were determined by gas-liquid chromatography; LDL receptor function was assayed as receptor-mediated binding of 125I-labeled LDL to mucosal membranes. Feeding 2% sitosterol or 0.04% lovastatin for 1 week significantly (P < 0.01) decreased the amounts of cholesterol absorbed per day (−85% and −63%, respectively). In contrast, feeding 2% cholesterol for 1 week increased the amounts of absorbed cholesterol 27-fold, even though the percent absorption significantly decreased. With all three treatments, there was a coordinate regulation of total HMG-CoA reductase activity and receptor-mediated LDL binding. Cholesterol feeding downregulated both total jejunal HMG-CoA reductase activity (P < 0.05) and receptor-mediated LDL binding (P < 0.01), whereas lovastatin- and sitosterol-supplemented diets significantly upregulated both of these parameters. In the control, cholesterol-fed, and sitosterol-fed animals, about half of the total jejunal HMG-CoA reductase activity was expressed (in functional dephosphorylated form). However, in the lovastatin-treated rats with 4-fold stimulation of HMG-CoA reductase, only 23% of the total enzyme activity was expressed. Changes in total HMG-CoA reductase activity and receptor-mediated LDL binding in all tested groups occurred with no change in total concentrations of mucosal cholesterol, and only cholesterol-fed animals had increased mucosal esterified cholesterol concentrations. Thus, in response to various fluxes of dietary or newly formed cholesterol, HMG-CoA reductase and receptor-mediated LDL binding are coordinately regulated to maintain constant cellular cholesterol concentrations in the jejunum. —Nguyen, L. B., S. Shefer, G. Salen, G. S. Tint, F. Ruiz, and J. Bullock. Mechanisms for cholesterol homeostasis in rat jejunal mucosa: effects of cholesterol, sitosterol, and lovastatin.http://www.sciencedirect.com/science/article/pii/S0022227520316795cholesterol absorptionintestinal cholesterol biosynthesisLDL receptorcholesterol uptakeLDL bindingHMG-CoA reductase
collection DOAJ
language English
format Article
sources DOAJ
author Lien B. Nguyen
Sarah Shefer
Gerald Salen
G.S. Tint
Frank Ruiz
John Bullock
spellingShingle Lien B. Nguyen
Sarah Shefer
Gerald Salen
G.S. Tint
Frank Ruiz
John Bullock
Mechanisms for cholesterol homeostasis in rat jejunal mucosa: effects of cholesterol, sitosterol, and lovastatin
Journal of Lipid Research
cholesterol absorption
intestinal cholesterol biosynthesis
LDL receptor
cholesterol uptake
LDL binding
HMG-CoA reductase
author_facet Lien B. Nguyen
Sarah Shefer
Gerald Salen
G.S. Tint
Frank Ruiz
John Bullock
author_sort Lien B. Nguyen
title Mechanisms for cholesterol homeostasis in rat jejunal mucosa: effects of cholesterol, sitosterol, and lovastatin
title_short Mechanisms for cholesterol homeostasis in rat jejunal mucosa: effects of cholesterol, sitosterol, and lovastatin
title_full Mechanisms for cholesterol homeostasis in rat jejunal mucosa: effects of cholesterol, sitosterol, and lovastatin
title_fullStr Mechanisms for cholesterol homeostasis in rat jejunal mucosa: effects of cholesterol, sitosterol, and lovastatin
title_full_unstemmed Mechanisms for cholesterol homeostasis in rat jejunal mucosa: effects of cholesterol, sitosterol, and lovastatin
title_sort mechanisms for cholesterol homeostasis in rat jejunal mucosa: effects of cholesterol, sitosterol, and lovastatin
publisher Elsevier
series Journal of Lipid Research
issn 0022-2275
publishDate 2001-02-01
description The effects of feeding cholesterol, sitosterol, and lovastatin on cholesterol absorption, biosynthesis, esterification, and LDL receptor function were examined in the rat jejunal mucosa. Cholesterol absorption was measured by the dual-isotope plasma ratio method; the rate-limiting enzyme of cholesterol biosynthesis, 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, was measured as total and expressed enzyme activities (in the absence and presence of a phosphatase inhibitor, NaF, respectively); mucosal total and esterified cholesterol concentrations were determined by gas-liquid chromatography; LDL receptor function was assayed as receptor-mediated binding of 125I-labeled LDL to mucosal membranes. Feeding 2% sitosterol or 0.04% lovastatin for 1 week significantly (P < 0.01) decreased the amounts of cholesterol absorbed per day (−85% and −63%, respectively). In contrast, feeding 2% cholesterol for 1 week increased the amounts of absorbed cholesterol 27-fold, even though the percent absorption significantly decreased. With all three treatments, there was a coordinate regulation of total HMG-CoA reductase activity and receptor-mediated LDL binding. Cholesterol feeding downregulated both total jejunal HMG-CoA reductase activity (P < 0.05) and receptor-mediated LDL binding (P < 0.01), whereas lovastatin- and sitosterol-supplemented diets significantly upregulated both of these parameters. In the control, cholesterol-fed, and sitosterol-fed animals, about half of the total jejunal HMG-CoA reductase activity was expressed (in functional dephosphorylated form). However, in the lovastatin-treated rats with 4-fold stimulation of HMG-CoA reductase, only 23% of the total enzyme activity was expressed. Changes in total HMG-CoA reductase activity and receptor-mediated LDL binding in all tested groups occurred with no change in total concentrations of mucosal cholesterol, and only cholesterol-fed animals had increased mucosal esterified cholesterol concentrations. Thus, in response to various fluxes of dietary or newly formed cholesterol, HMG-CoA reductase and receptor-mediated LDL binding are coordinately regulated to maintain constant cellular cholesterol concentrations in the jejunum. —Nguyen, L. B., S. Shefer, G. Salen, G. S. Tint, F. Ruiz, and J. Bullock. Mechanisms for cholesterol homeostasis in rat jejunal mucosa: effects of cholesterol, sitosterol, and lovastatin.
topic cholesterol absorption
intestinal cholesterol biosynthesis
LDL receptor
cholesterol uptake
LDL binding
HMG-CoA reductase
url http://www.sciencedirect.com/science/article/pii/S0022227520316795
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