Role of thyroid hormone in hepatic gene regulation, chromatin remodeling, and autophagy

Thyroid hormone (TH) actions on development and metabolism have been studied ever since the discovery of thyroxine almost a century ago. Initial studies focused on the physiological and biochemical actions of TH. Later, the cloning of the thyroid hormone receptor (THR) isoforms and the development of techniques enabled the study of TH regulation of complex cellular processes (such as gene transcription). Recently we found that TH activates secondary transcription factors such as FOXO1, to amplify gene transcription; and also is a potent inducer of autophagy that was critical for fatty acid β-oxidation in the liver. This review summarizes the recent advancements in our understanding of TH regulation of gene expression of metabolic genes (via co-regulators/transcription factors and epigenetic control) and autophagy in the liver. Our deeper understanding of TH action recently has led to the development of tissue- and THR isoform-specific TH mimetics that may be useful for the treatment of metabolic disorders.