Thyroid hormone enhances the ability of serum to accept cellular cholesterol via the ABCA1 transporter

ObjectiveThe goal of this study was to examine the effects of thyroid hormone status on the ability of serum to accept cellular cholesterol.Methods and resultsSera from hypophysectomized rats treated ±T3 was used to evaluate the role of thyroid hormone on serum efflux capacity. 2D-DIGE analysis of serum proteins showed that T3 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 T3. 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 T3-treated rats stimulated efflux via ABCA1 but not by ABCG1 or SR-BI. Gel filtration chromatography revealed that T3 treatment caused a decrease in HDL particle size accompanied by higher levels of lipid-poor ApoA-I.ConclusionsThyroid 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 T3.