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...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2001-02-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520316795 |
| _version_ | 1818931351971168256 |
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| author | Lien B. Nguyen Sarah Shefer Gerald Salen G.S. Tint Frank Ruiz John Bullock |
| author_facet | Lien B. Nguyen Sarah Shefer Gerald Salen G.S. Tint Frank Ruiz John Bullock |
| author_sort | Lien B. Nguyen |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-20T04:15:13Z |
| format | Article |
| id | doaj.art-fe2ec2f5c03d4b7fbbb09e3bb8d73a77 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-20T04:15:13Z |
| publishDate | 2001-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-fe2ec2f5c03d4b7fbbb09e3bb8d73a772022-12-21T19:53:48ZengElsevierJournal 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 |
| 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 |
| title | 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_short | 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 |
| 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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