It was discovered that insulin binding to insulin receptors signals the upregulation of expression of the liver enzyme deiodinase 1 (Dio1), which in turn activates the ApoA-1 promoter, thereby thereby increasing ApoA-1 expression (primarily in the liver), that in turn raises the levels of plasma ApoA-1, the major and necessary protein in HDLC. Certain embodiments of the invention are directed to methods for increasing circulating HDLC levels in an animal by administering therapeutically effective amounts of Dio1, or by increasing the level of Dio1 through gene therapy.