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 T(3) 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 7alpha-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 [(3)H]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.
Tancevski
Ivan
I
Department of Internal Medicine, Innsbruck Medical University, Anichstrasse 35, Innsbruck, Austria. ivan.tancevski@i-med.ac.at
Wehinger
Andreas
A
Demetz
Egon
E
Eller
Philipp
P
Duwensee
Kristina
K
Huber
Julia
J
Hochegger
Kathrin
K
Schgoer
Wilfried
W
Fievet
Catherine
C
Stellaard
Frans
F
Rudling
Mats
M
Patsch
Josef R
JR
Ritsch
Andreas
A
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001646:Bile / Q000737:chemistry; D015153:Blotting, Western; D002784:Cholesterol / Q000378:metabolism; D008076:Cholesterol, HDL / Q000097:blood*; D005243:Feces / Q000737:chemistry; D015870:Gene Expression; D006980:Hyperthyroidism / Q000097:blood / Q000378:metabolism / Q000503:physiopathology*; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D020133:Reverse Transcriptase Polymerase Chain Reaction
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D008076:Cholesterol, HDL; D002784:Cholesterol