This narrative review examines the role of thyroid hormones (TH) in regulating hepatic energy metabolism, integrating effects of nutritional interventions like fasting and diets. The background establishes the liver as a central organ for energy homeostasis, where local TH action via nuclear receptors (TRs) and deiodinases (Dios) modulates glucose, lipid, and cholesterol metabolism. Methods involve summarizing data from animal models (rodents) and cell culture systems, with some human data for comparison. Key results show that fasting reduces systemic and hepatic TH concentrations, altering deiodinase activity (e.g., decreased Dio1, increased Dio3) and TH transporter expression (e.g., Mct10, Ntcp). Dietary interventions like high-fat diets can induce Dio1 and affect TH-responsive genes. Direct TH effects include regulation of gluconeogenesis (via PCK1, G6PC), de novo lipogenesis (via Fasn, Acc1, Spot14), fatty acid oxidation (via CPT1A, PGC1α), and cholesterol metabolism (via HMG-CoA reductase, LDLR, CYP7A1). Limitations include species-specific differences (e.g., rat vs. mouse fasting responses), the predominance of preclinical data, and the need for cell-type-specific studies in liver diseases like NAFLD/NASH. Implications suggest that understanding local hepatic TH regulation could inform therapeutic strategies using TRβ-selective thyromimetics for metabolic disorders, though translational evidence remains indirect.
