Journal of Lipid Research (May 2003)
Hypercholesterolemia and changes in lipid and bile acid metabolism in male and female cyp7A1-deficient mice
- 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
Affiliations
- Sandra K. Erickson
- Department 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 07018
- Steven R. Lear
- Department 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 07018
- Sean Deane
- Department 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 07018
- Sandrine Dubrac
- Department 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 07018
- Sandra L. Huling
- Department 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 07018
- Lien Nguyen
- Department 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 07018
- Jaya S. Bollineni
- Department 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 07018
- Sarah Shefer
- Department 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 07018
- Hideyuki Hyogo
- Department 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 07018
- David E. Cohen
- Department 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 07018
- Benjamin Shneider
- Department 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 07018
- Ephraim Sehayek
- Department 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 07018
- Meena Ananthanarayanan
- Department 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 07018
- Natarajan Balasubramaniyan
- Department 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 07018
- Fredrick J. Suchy
- Department 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 07018
- Ashok K. Batta
- Department 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 07018
- Gerald Salen
- Department 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 07018
- Journal volume & issue
-
Vol. 44,
no. 5
pp. 1001 – 1009
Abstract
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.
