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Reduced Plasma High-Density Lipoprotein Cholesterol in Hyperthyroid Mice Coincides with Decreased Hepatic Adenosine 5'-Triphosphate-Binding Cassette Transporter 1 Expression

Department of Internal Medicine (I.T., A.W., E.D., P.E., K.D., J.H., K.H., W.S., J.R.P., A.R.), Innsbruck Medical University, A-6020 Innsbruck, Austria; Institut Pasteur de Lille (C.F.), Département d’Athérosclérose, and Institut National de la Santé et de la Recherche Médicale (C.F.), Unité 545, Lille F-59019, France; Université de Lille 2 (C.F.), Faculté des Sciences Pharmaceutiques et Biologiques et Faculté de Médecine, Lille F-59006, France; Laboratory of Pediatrics (F.S.), Center for Liver, Digestive and Metabolic Diseases, University Medical Center Groningen, 9700 Groningen, The Netherlands; and Karolinska Institute at Center for Endocrinology, Metabolism and Diabetes (M.R.), Department of Medicine, Karolinska University Hospital, and Molecular Nutrition Unit, Center for Nutrition and Toxicology, SE-171 77 Stockholm, Sweden

Address all correspondence and requests for reprints to: Ivan Tancevski, Department of Internal Medicine, Innsbruck Medical University, Anichstrasse 35, A-6020 Innsbruck, Austria. E-mail: ivan.tancevski{at}i-med.ac.at.

The aim of the study was to investigate the influence of severe hyperthyroidism on plasma high-density lipoprotein cholesterol (HDL-C). Recently, it was shown in mice that increasing doses of T₃ up-regulate hepatic expression of scavenger receptor class B, type I, resulting in increased clearance of plasma HDL-C. Here, we show that severe hyperthyroidism in mice did not affect hepatic expression of scavenger receptor class B, type I, but reduced hepatic expression of ATP-binding cassette transporter 1, accompanied by a 40% reduction of HDL-C. The sterol content of bile, liver, and feces was markedly increased, accompanied by up-regulation of hepatic cholesterol 7-hydroxylase, and ATP-binding cassette transporter 5, which is known to promote biliary sterol secretion upon dimerization with ATP-binding cassette transporter 8. Both control and hyperthyroid mice exerted identical plasma clearance of iv injected [³H]HDL-C, supporting the view that severe hyperthyroidism does not affect HDL-C clearance but, rather, its formation via hepatic ATP-binding cassette transporter 1.