Thyroid hormone is a critical modulator of brain metabolism, and it is highly controlled in the central nervous system. Recent research has uncovered an important role of thyroid hormone in the regulation of fatty acid oxidation (FAO), an energetic process essential for neurodevelopment that continues to support brain metabolism during adulthood. Thyroid hormone stimulation of FAO has been shown to be protective in astrocytes and mouse models of brain injury, yet a clear mechanism of this relationship has not been elucidated. Thyroid hormone interacts with multiple receptors located in the nucleus and the mitochondria, initiating rapid and long-term effects via both genomic and nongenomic pathways. This has complicated efforts to isolate and study-specific interactions. This chapter presents the primary signaling pathways that have been identified to play a role in the thyroid hormone-mediated increase in FAO. Investigation of the impact of thyroid hormone on FAO in the adult brain has challenged classical models of brain metabolism and widened the window of potential neuroprotective strategies. A detailed understanding of these pathways is essential for any researchers aiming to expand the field of neuroenergetics.
Keywords: Astrocytes; Brain metabolism; Carnitine palmitoyl transferase; Fatty acid oxidation; Long chain fatty acids; Mitochondrial trifunctional protein; Nonthyroidal illness syndrome; Thyroid hormone.
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