Table 2.
Common themes integrating thyroid hormone metabolic regulation
| Metabolic Regulatory Themes | Thyroid Hormone Action | Central Regulation of Thyroid Hormone Production | Thermogenesis and Body Weight | Cholesterol and Triglyceride Regulation | Carbohydrate Metabolism |
|---|---|---|---|---|---|
| Nutrient feedback | Histone modification (165) | Leptin feedback to arcuate nucleus (117) | T3 regulation of BMR (137) | Crosstalk with LXR (110) | Crosstalk with LXR (147) |
| Sirtuin expression | Selenium required for D2 activity (90) | Fat intake | Crosstalk with PPARα, γ, δ (157, 158) | Fat intake | |
| Nongenomic signal transduction pathways (34) | Carbohydrate intake | Bile acid and increased thermogenesis (269) | Carbohydrate intake | ||
| Coregulator recruitment (71, 165) | Body composition | TGR5 receptor in white adipose (246) | |||
| Nuclear corepressor action | Mediates basal repression and ligand-induced gene activation or repression (185) | NCoR/HDAC3 and TSH regulation (11, 276) | Modulation of UCP1 expression | Modulation of gene regulation by TR in liver and white adipose (283) | Modulation of gene regulation by TR in liver and white adipose, BAT, and pancreas |
| Truncated forms of NCoR/SMRT regulate adipocyte differentiation (98) | |||||
| Adrenergic sensitivity | TRα adipocyte lipolysis (160) | Central adrenergic regulation of thermogenesis (163) | D2 activation by stimulating deubiquitinase (212) | T3 potentiation of catecholamine-induced lipolysis (160) | Suppresses insulin secretion and increases glycogenolysis |
| TRα BAT thermogenesis (207) | Central regulation of cardiovascular function in PBN (179) | Synergistic with T3 in stimulation of UCP1 expression (19) | |||
| Local ligand availability | D2 expression in inner ear and retinal development (186) | D2 activity in the hypothalamus (79) | BAT thermogenesis | Bile acid stimulation of D2 expression (269) | D2 requirement for pancreatic islet function (3) |
| Induction of D2 for T3 activation or D3 for inactivation (90, 149) | D2 and T4/TSH set point (116) | Greater weight loss with T3 replacement compared with T4 (37) | D2 polymorphisms in diabetes (70, 174) |
BAT, brown adipose tissue; D2, 5′-deiodinase type 2; HDAC3, histone deacetylase 3; LXR, liver X receptor; NCoR, nuclear corepressor; PBN, parvalbuminergic neurons in anterior hypothalamus; PPARα, peroxisome proliferator-activated receptor; RXR, retinoid X receptor; SMRT, silencing mediator for retinoic and thyroid hormone receptor; T3, triiodothyronine; T4, thyroxine; TGR5, G protein-coupled receptor bile acid receptor; TR, thyroid hormone receptor; TRH, thyrotropin-releasing hormone; TSH, thyroid-stimulating hormone; UCP1, uncoupling protein 1. Reference numbers are in parentheses.