Table 1.
Sites of thyroid hormone action in metabolic regulation
| Process | Elements That Regulate Metabolism | Basic Mechanisms | Examples of Physiological Actions | Reference Nos. |
|---|---|---|---|---|
| Thyroid hormone action | TR isoforms | TR isoform specificity | Increased basal metabolic rate (BMR) | 27, 39, 159, 232 |
| Corepressor action (NCoR and SMRT) | Histone modification | Stimulate lipolysis/lipogenesis | ||
| Nutrient feedback | Sumoylation | Increase in adaptive thermogenesis | ||
| Nongenomic action | Corepressor interactions | Stimulate β-oxidation of fatty acids | ||
| Tissue-selective thyroid hormone transport | Modulation of signal transduction pathways | |||
| Stimulation of Na+-K+-ATPase and SERCA1 | ||||
| Central regulation of TRH/TSH | T4/T3 feedback | Integration of TRH/TSH regulation with metabolic signals | TSH measurement for the diagnosis of thyroid disease | 117, 163 |
| Leptin | Thyroid hormone transport into the hypothalamus and pituitary (e.g., by MCT8) | And to monitor treatment | ||
| AMPK activation | Integration of adrenergic signaling | Central adaptation to fasting, illness, and obesity | ||
| Oxrexigenic/anorectic peptides/appetite regulation | ||||
| Thyronamines (T1AM) | ||||
| Circadian rhythms | ||||
| Local ligand activation by D2 | D2 expression and activity | Regulation of D2 ubiquitination/deubiquitination | TSH/T4 set point | 90, 149 |
| D2 polymorphisms | Increase in D2 activity with reduction in serum T4 concentration | T4/T3 replacement therapy of hypothyroidism | ||
| Selenium requirement for deiodinase activity | Developmental and tissue selective deiodinase expression | Stimulates adaptive thermogenesis | ||
| Thermogenesis and body weight | Basal metabolic rate | Integration of adrenergic signaling | Reduces body fat | 229 |
| Adaptive thermogenesis | Central and local adrenergic actions | Increases β-oxidation of fatty acids | ||
| Body weight and body composition | Stimulation of CPT1α expression | Stimulates adaptive thermogenesis | ||
| Appetite | Stimulattion of UCP1 expression | |||
| Cholesterol and triglycerides | Cholesterol synthesis | Stimulates LDL-R | Reduces serum cholesterol | 145, 157, 270 |
| Reverse cholesterol transport | Stimulates ABCA1 | Reduces serum triglycerides | ||
| Lipolysis/lipogenesis | Reduces hepatic steatosis | |||
| Hepatic steatosis | ||||
| Carbohydrate metabolism | Pancreatic islet development | TR expression in developing islets | Stimulates gluconeogenesis | 49 |
| Pancreatic islet proliferation | D2 required for developing islets and islet function | Reduces insulin sensitivity | ||
| Insulin production | Insulin signaling | Increase in insulin metabolism | ||
| Gluconeogenesis | Stimulation of mitochondrial respiration | |||
| Insulin sensitivity | Increase in expression of ChREBP, GLUT4, ACC1 | |||
| Insulin metabolism |
ABCA1, ATP-binding cassette transporter A1; ACC1, acetyl CoA carboxylase; ChREBP, carbohydrate response element binding protein; CPT-Iα, carnitine palmitoyltransferase Ia; CYP7A1, cholesterol 7-hydroxylase; D2, 5′-deiodinase type 2; GLUT4, glucose transporter 4; LDL-R, low-density lipoprotein receptor; LXR, liver X receptor; NCoR, nuclear corepressor; PPARα, peroxisome proliferator-activated receptor; RXR, retinoid X receptor; SERCA, sarcoplasmic reticulum calcium ATPase; SMRT, silencing mediator for retinoic and thyroid hormone receptor; T3, triiodothyronine; T4, thyroxine; TGR5, G protein-coupled receptor bile acid receptor; TRH, thyrotropin-releasing hormone; TSH, thyroid-stimulating hormone; UCP, uncoupling protein.