ABSTRACT
OBJECTIVE: The goal of this study was to examine the effects of thyroid hormone status on the ability of serum to accept cellular cholesterol. METHODS AND RESULTS: Sera from hypophysectomized rats treated ± T(3) was used to evaluate the role of thyroid hormone on serum efflux capacity. 2D-DIGE analysis of serum proteins showed that T(3) treated rats had increased ApoA-I, ApoA-IV and fetuin A levels with decreased Apo E levels. Microarray and real-time RT-PCR analysis of rat liver revealed large increases in ApoA-I, ApoA-IV, ABCG5, and ABCG8 in response to T(3). J774 macrophages, BHK cells, and Fu5AH rat hepatoma cells were used to measure cholesterol efflux mediated by ABCA1, ABCG1 transporters or SR-BI. Sera from T(3)-treated rats stimulated efflux via ABCA1 but not by ABCG1 or SR-BI. Gel filtration chromatography revealed that T(3) treatment caused a decrease in HDL particle size accompanied by higher levels of lipid-poor ApoA-I. CONCLUSIONS: Thyroid hormone enhances the ability of serum to accept cellular cholesterol via the ABCA1 transporter. This effect is most likely attributable to increases in small HDL and lipid poor ApoA-I in response to T(3).
