Type 1 Deiodinase Regulates ApoA-I Gene Expression and ApoA-I Synthesis Independent of Thyroid Hormone Signaling

• DOI: 10.1161/atvbaha.116.307330
• Publication Date: 2016-05-06T05:50:10Z
• Authors: Jing Liu; Antonio Hernandez...; Mark J. Graham; Valerie Anne Galton; Henry N. Ginsberg
• Keywords: DIO2; Iodothyronine deiodinase; Thyroid hormone receptor

Plasma levels of high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I (ApoA-I) are reduced in individuals with defective insulin signaling. Initial studies using liver-specific receptor (InsR) knockout mice identified expression type 1 deiodinase (Dio1) as a potentially novel link between hepatic signaling the ApoA-I gene. Our objective was to examine regulation by Dio1.Acute inactivation InsR adenoviral delivery Cre recombinase floxed HDL-C both Dio1. Overexpression Dio1 restored increased ApoA-I. had low serum Treatment C57BL/6J antisense mRNA, HDL-C, Hepatic 3,5,3'-triiodothyronine content normal or elevated mice. Knockdown either siRNA HepG2 cells decreased synthesis secretion. knockdown activity region promoter lacking thyroid hormone response elements (region B). Electrophoretic mobility shift assay demonstrated that binding nuclear proteins B.Reductions reduce 3,5,3'-triiodothyronine-/thyroid element-independent manner.