Reduced plasma high-density lipoprotein cholesterol in hyperthyroid mice coincides with decreased hepatic adenosine 5'-triphosphate-binding cassette transporter 1 expression

• 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 7α-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.

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