Hypercholesterolemia and changes in lipid and bile acid metabolism in male and female cyp7A1-deficient mice
Cholesterol 7α-hydroxylase, a rate-limiting enzyme for bile acid synthesis, has been implicated in genetic susceptibility to atherosclerosis. The gene, CYP7A1, encoding a protein with this activity, is expressed normally only in hepatocytes and is highly regulated. Our cyp7A1 gene knockout mouse col...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2003-05-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520311469 |
| _version_ | 1818936729406537728 |
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| author | Sandra K. Erickson Steven R. Lear Sean Deane Sandrine Dubrac Sandra L. Huling Lien Nguyen Jaya S. Bollineni Sarah Shefer Hideyuki Hyogo David E. Cohen Benjamin Shneider Ephraim Sehayek Meena Ananthanarayanan Natarajan Balasubramaniyan Fredrick J. Suchy Ashok K. Batta Gerald Salen |
| author_facet | Sandra K. Erickson Steven R. Lear Sean Deane Sandrine Dubrac Sandra L. Huling Lien Nguyen Jaya S. Bollineni Sarah Shefer Hideyuki Hyogo David E. Cohen Benjamin Shneider Ephraim Sehayek Meena Ananthanarayanan Natarajan Balasubramaniyan Fredrick J. Suchy Ashok K. Batta Gerald Salen |
| author_sort | Sandra K. Erickson |
| collection | DOAJ |
| description | Cholesterol 7α-hydroxylase, a rate-limiting enzyme for bile acid synthesis, has been implicated in genetic susceptibility to atherosclerosis. The gene, CYP7A1, encoding a protein with this activity, is expressed normally only in hepatocytes and is highly regulated. Our cyp7A1 gene knockout mouse colony, as young adults on a chow diet, is hypercholesterolemic. These mice were characterized extensively to understand how cyp7A1 affects lipid and bile acid homeostasis in different tissue compartments and whether gender plays a modifying role. Both male and female cyp7A1-deficient mice had decreased hepatic LDL receptors, unchanged hepatic cholesterol synthesis, increased intestinal cholesterol synthesis and bile acid transporters, and decreased fecal bile acids but increased fecal sterols. In females, cyp7A1 deficiency also caused changes in hepatic fatty acid metabolism, decreased hepatic canalicular bile acid transporter, Bsep, and gallbladder bile composition altered to a lithogenic profile.Taken together, the data suggest that cyp7A1 deficiency results in a proatherogenic phenotype in both genders and leads to a prolithogenic phenotype in females. |
| first_indexed | 2024-12-20T05:40:41Z |
| format | Article |
| id | doaj.art-b1870655655549448295e9a0ea9dcbd8 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-20T05:40:41Z |
| publishDate | 2003-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-b1870655655549448295e9a0ea9dcbd82022-12-21T19:51:28ZengElsevierJournal of Lipid Research0022-22752003-05-0144510011009Hypercholesterolemia and changes in lipid and bile acid metabolism in male and female cyp7A1-deficient miceSandra K. Erickson0Steven R. Lear1Sean Deane2Sandrine Dubrac3Sandra L. Huling4Lien Nguyen5Jaya S. Bollineni6Sarah Shefer7Hideyuki Hyogo8David E. Cohen9Benjamin Shneider10Ephraim Sehayek11Meena Ananthanarayanan12Natarajan Balasubramaniyan13Fredrick J. Suchy14Ashok K. Batta15Gerald Salen16Department of Medicine, University of California, San Francisco, CA 94143; Liver Center, University of California, San Francisco, CA 94143; Department of Veterans Affairs, San Francisco, CA 94121; Department of Medicine and Liver Center, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103; Department of Medicine and Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY 10461; Department of Pediatrics, Mount Sinai Medical Center, New York, NY 10029; Department of Medicine, Rockefeller University, New York, NY 10021; GI Research Laboratory, Veterans Affairs Medical Center, East Orange, NJ 07018Department of Medicine, University of California, San Francisco, CA 94143; Liver Center, University of California, San Francisco, CA 94143; Department of Veterans Affairs, San Francisco, CA 94121; Department of Medicine and Liver Center, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103; Department of Medicine and Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY 10461; Department of Pediatrics, Mount Sinai Medical Center, New York, NY 10029; Department of Medicine, Rockefeller University, New York, NY 10021; GI Research Laboratory, Veterans Affairs Medical Center, East Orange, NJ 07018Department of Medicine, University of California, San Francisco, CA 94143; Liver Center, University of California, San Francisco, CA 94143; Department of Veterans Affairs, San Francisco, CA 94121; Department of Medicine and Liver Center, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103; Department of Medicine and Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY 10461; Department of Pediatrics, Mount Sinai Medical Center, New York, NY 10029; Department of Medicine, Rockefeller University, New York, NY 10021; GI Research Laboratory, Veterans Affairs Medical Center, East Orange, NJ 07018Department of Medicine, University of California, San Francisco, CA 94143; Liver Center, University of California, San Francisco, CA 94143; Department of Veterans Affairs, San Francisco, CA 94121; Department of Medicine and Liver Center, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103; Department of Medicine and Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY 10461; Department of Pediatrics, Mount Sinai Medical Center, New York, NY 10029; Department of Medicine, Rockefeller University, New York, NY 10021; GI Research Laboratory, Veterans Affairs Medical Center, East Orange, NJ 07018Department of Medicine, University of California, San Francisco, CA 94143; Liver Center, University of California, San Francisco, CA 94143; Department of Veterans Affairs, San Francisco, CA 94121; Department of Medicine and Liver Center, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103; Department of Medicine and Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY 10461; Department of Pediatrics, Mount Sinai Medical Center, New York, NY 10029; Department of Medicine, Rockefeller University, New York, NY 10021; GI Research Laboratory, Veterans Affairs Medical Center, East Orange, NJ 07018Department of Medicine, University of California, San Francisco, CA 94143; Liver Center, University of California, San Francisco, CA 94143; Department of Veterans Affairs, San Francisco, CA 94121; Department of Medicine and Liver Center, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103; Department of Medicine and Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY 10461; Department of Pediatrics, Mount Sinai Medical Center, New York, NY 10029; Department of Medicine, Rockefeller University, New York, NY 10021; GI Research Laboratory, Veterans Affairs Medical Center, East Orange, NJ 07018Department of Medicine, University of California, San Francisco, CA 94143; Liver Center, University of California, San Francisco, CA 94143; Department of Veterans Affairs, San Francisco, CA 94121; Department of Medicine and Liver Center, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103; Department of Medicine and Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY 10461; Department of Pediatrics, Mount Sinai Medical Center, New York, NY 10029; Department of Medicine, Rockefeller University, New York, NY 10021; GI Research Laboratory, Veterans Affairs Medical Center, East Orange, NJ 07018Department of Medicine, University of California, San Francisco, CA 94143; Liver Center, University of California, San Francisco, CA 94143; Department of Veterans Affairs, San Francisco, CA 94121; Department of Medicine and Liver Center, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103; Department of Medicine and Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY 10461; Department of Pediatrics, Mount Sinai Medical Center, New York, NY 10029; Department of Medicine, Rockefeller University, New York, NY 10021; GI Research Laboratory, Veterans Affairs Medical Center, East Orange, NJ 07018Department of Medicine, University of California, San Francisco, CA 94143; Liver Center, University of California, San Francisco, CA 94143; Department of Veterans Affairs, San Francisco, CA 94121; Department of Medicine and Liver Center, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103; Department of Medicine and Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY 10461; Department of Pediatrics, Mount Sinai Medical Center, New York, NY 10029; Department of Medicine, Rockefeller University, New York, NY 10021; GI Research Laboratory, Veterans Affairs Medical Center, East Orange, NJ 07018Department of Medicine, University of California, San Francisco, CA 94143; Liver Center, University of California, San Francisco, CA 94143; Department of Veterans Affairs, San Francisco, CA 94121; Department of Medicine and Liver Center, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103; Department of Medicine and Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY 10461; Department of Pediatrics, Mount Sinai Medical Center, New York, NY 10029; Department of Medicine, Rockefeller University, New York, NY 10021; GI Research Laboratory, Veterans Affairs Medical Center, East Orange, NJ 07018Department of Medicine, University of California, San Francisco, CA 94143; Liver Center, University of California, San Francisco, CA 94143; Department of Veterans Affairs, San Francisco, CA 94121; Department of Medicine and Liver Center, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103; Department of Medicine and Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY 10461; Department of Pediatrics, Mount Sinai Medical Center, New York, NY 10029; Department of Medicine, Rockefeller University, New York, NY 10021; GI Research Laboratory, Veterans Affairs Medical Center, East Orange, NJ 07018Department of Medicine, University of California, San Francisco, CA 94143; Liver Center, University of California, San Francisco, CA 94143; Department of Veterans Affairs, San Francisco, CA 94121; Department of Medicine and Liver Center, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103; Department of Medicine and Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY 10461; Department of Pediatrics, Mount Sinai Medical Center, New York, NY 10029; Department of Medicine, Rockefeller University, New York, NY 10021; GI Research Laboratory, Veterans Affairs Medical Center, East Orange, NJ 07018Department of Medicine, University of California, San Francisco, CA 94143; Liver Center, University of California, San Francisco, CA 94143; Department of Veterans Affairs, San Francisco, CA 94121; Department of Medicine and Liver Center, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103; Department of Medicine and Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY 10461; Department of Pediatrics, Mount Sinai Medical Center, New York, NY 10029; Department of Medicine, Rockefeller University, New York, NY 10021; GI Research Laboratory, Veterans Affairs Medical Center, East Orange, NJ 07018Department of Medicine, University of California, San Francisco, CA 94143; Liver Center, University of California, San Francisco, CA 94143; Department of Veterans Affairs, San Francisco, CA 94121; Department of Medicine and Liver Center, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103; Department of Medicine and Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY 10461; Department of Pediatrics, Mount Sinai Medical Center, New York, NY 10029; Department of Medicine, Rockefeller University, New York, NY 10021; GI Research Laboratory, Veterans Affairs Medical Center, East Orange, NJ 07018Department of Medicine, University of California, San Francisco, CA 94143; Liver Center, University of California, San Francisco, CA 94143; Department of Veterans Affairs, San Francisco, CA 94121; Department of Medicine and Liver Center, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103; Department of Medicine and Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY 10461; Department of Pediatrics, Mount Sinai Medical Center, New York, NY 10029; Department of Medicine, Rockefeller University, New York, NY 10021; GI Research Laboratory, Veterans Affairs Medical Center, East Orange, NJ 07018Department of Medicine, University of California, San Francisco, CA 94143; Liver Center, University of California, San Francisco, CA 94143; Department of Veterans Affairs, San Francisco, CA 94121; Department of Medicine and Liver Center, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103; Department of Medicine and Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY 10461; Department of Pediatrics, Mount Sinai Medical Center, New York, NY 10029; Department of Medicine, Rockefeller University, New York, NY 10021; GI Research Laboratory, Veterans Affairs Medical Center, East Orange, NJ 07018Department of Medicine, University of California, San Francisco, CA 94143; Liver Center, University of California, San Francisco, CA 94143; Department of Veterans Affairs, San Francisco, CA 94121; Department of Medicine and Liver Center, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103; Department of Medicine and Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY 10461; Department of Pediatrics, Mount Sinai Medical Center, New York, NY 10029; Department of Medicine, Rockefeller University, New York, NY 10021; GI Research Laboratory, Veterans Affairs Medical Center, East Orange, NJ 07018Cholesterol 7α-hydroxylase, a rate-limiting enzyme for bile acid synthesis, has been implicated in genetic susceptibility to atherosclerosis. The gene, CYP7A1, encoding a protein with this activity, is expressed normally only in hepatocytes and is highly regulated. Our cyp7A1 gene knockout mouse colony, as young adults on a chow diet, is hypercholesterolemic. These mice were characterized extensively to understand how cyp7A1 affects lipid and bile acid homeostasis in different tissue compartments and whether gender plays a modifying role. Both male and female cyp7A1-deficient mice had decreased hepatic LDL receptors, unchanged hepatic cholesterol synthesis, increased intestinal cholesterol synthesis and bile acid transporters, and decreased fecal bile acids but increased fecal sterols. In females, cyp7A1 deficiency also caused changes in hepatic fatty acid metabolism, decreased hepatic canalicular bile acid transporter, Bsep, and gallbladder bile composition altered to a lithogenic profile.Taken together, the data suggest that cyp7A1 deficiency results in a proatherogenic phenotype in both genders and leads to a prolithogenic phenotype in females.http://www.sciencedirect.com/science/article/pii/S0022227520311469liverintestinelipid synthesislow density lipoprotein receptorssterol 27-hydroxylasebile acid transporters |
| spellingShingle | Sandra K. Erickson Steven R. Lear Sean Deane Sandrine Dubrac Sandra L. Huling Lien Nguyen Jaya S. Bollineni Sarah Shefer Hideyuki Hyogo David E. Cohen Benjamin Shneider Ephraim Sehayek Meena Ananthanarayanan Natarajan Balasubramaniyan Fredrick J. Suchy Ashok K. Batta Gerald Salen Hypercholesterolemia and changes in lipid and bile acid metabolism in male and female cyp7A1-deficient mice Journal of Lipid Research liver intestine lipid synthesis low density lipoprotein receptors sterol 27-hydroxylase bile acid transporters |
| title | Hypercholesterolemia and changes in lipid and bile acid metabolism in male and female cyp7A1-deficient mice |
| title_full | Hypercholesterolemia and changes in lipid and bile acid metabolism in male and female cyp7A1-deficient mice |
| title_fullStr | Hypercholesterolemia and changes in lipid and bile acid metabolism in male and female cyp7A1-deficient mice |
| title_full_unstemmed | Hypercholesterolemia and changes in lipid and bile acid metabolism in male and female cyp7A1-deficient mice |
| title_short | Hypercholesterolemia and changes in lipid and bile acid metabolism in male and female cyp7A1-deficient mice |
| title_sort | hypercholesterolemia and changes in lipid and bile acid metabolism in male and female cyp7a1 deficient mice |
| topic | liver intestine lipid synthesis low density lipoprotein receptors sterol 27-hydroxylase bile acid transporters |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520311469 |
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