Significance of thyroid hormone receptor α in metabolism
Thyroid hormone (TH) is long known for its profound effects on metabolism. Novel studies have revealed that these effects are not restricted to the cellular and organ level, and that TH also affects metabolism by altering the autonomic nervous system via TH receptor α1. Mice expressing a mutant R384C TH receptor α1 display a central sympathetic hyperactivation of their brown adipose tissue, which causes severe hypermetabolism and resistance to high-fat diet-induced obesity. Moreover, the autonomic control of cardiac activity is also impaired and the mice fail to adapt their heart rate to environmental changes. Analysis of hepatic glucose metabolism and glycogen storage, both severely disrupted in the mutant animals, revealed that this defect that is founded during the embryonal development of the autonomic nervous system. Although the precise mechanism remains yet to be elucidated, several dysregulated genes such as KCNA1 and Atp1a2 have been identified in the hypothalamus of these mice, which could constitute the missing link between TH and the development of the autonomic nervous system.