Thyroid Hormone Regulation of Metabolism

Published on Apr 1, 2014in Physiological Reviews37.312
· DOI :10.1152/PHYSREV.00030.2013
Rashmi S. Mullur5
Estimated H-index: 5
(UCLA: University of California, Los Angeles),
Yan-Yun Liu14
Estimated H-index: 14
(UCLA: University of California, Los Angeles),
Gregory A. Brent43
Estimated H-index: 43
(UCLA: University of California, Los Angeles)
Thyroid hormone (TH) is required for normal development as well as regulating metabolism in the adult. The thyroid hormone receptor (TR) isoforms, α and β, are differentially expressed in tissues and have distinct roles in TH signaling. Local activation of thyroxine (T4), to the active form, triiodothyronine (T3), by 5′-deiodinase type 2 (D2) is a key mechanism of TH regulation of metabolism. D2 is expressed in the hypothalamus, white fat, brown adipose tissue (BAT), and skeletal muscle and is required for adaptive thermogenesis. The thyroid gland is regulated by thyrotropin releasing hormone (TRH) and thyroid stimulating hormone (TSH). In addition to TRH/TSH regulation by TH feedback, there is central modulation by nutritional signals, such as leptin, as well as peptides regulating appetite. The nutrient status of the cell provides feedback on TH signaling pathways through epigentic modification of histones. Integration of TH signaling with the adrenergic nervous system occurs peripherally, in liver, white fat, and BAT, but also centrally, in the hypothalamus. TR regulates cholesterol and carbohydrate metabolism through direct actions on gene expression as well as cross-talk with other nuclear receptors, including peroxisome proliferator-activated receptor (PPAR), liver X receptor (LXR), and bile acid signaling pathways. TH modulates hepatic insulin sensitivity, especially important for the suppression of hepatic gluconeogenesis. The role of TH in regulating metabolic pathways has led to several new therapeutic targets for metabolic disorders. Understanding the mechanisms and interactions of the various TH signaling pathways in metabolism will improve our likelihood of identifying effective and selective targets.
📖 Papers frequently viewed together
12 Authors (Ross L. Prentice)
#1Subhamoy Dasgupta (BCM: Baylor College of Medicine)H-Index: 17
#2David M. LonardH-Index: 33
Last. Bert W. O'Malley (BCM: Baylor College of Medicine)H-Index: 51
view all 3 authors...
Transcriptional coregulators (coactivators and corepressors) have emerged as the principal modulators of the functions of nuclear receptors and other transcription factors. During the decade since the discovery of steroid receptor coactivator-1 (SRC-1), the first authentic coregulator, more than 400 coregulators have been identified and characterized, and deciphering their function has contributed significantly to our understanding of their role in human physiology. Deregulated expression of cor...
#1Ann Marie Zavacki (Brigham and Women's Hospital)H-Index: 33
#2P. Reed Larsen (Brigham and Women's Hospital)H-Index: 71
The article by van Mullem et al in this issue of the JCEM (1) provides additional information about the clinical characteristics of 2 of the first 3 individuals recently identified to have resistance to thyroid hormone (RTH) due to a mutation in the thyroid hormone receptor α (TRα) 1 (2, 3). In this editorial discussing this newly recognized phenotype, we will use the term RTHα to distinguish it from RTH due to mutations in the thyroid hormone receptor β isoform (RTHβ). A brief review of thyroid...
#1W. Edward Visser (EUR: Erasmus University Rotterdam)H-Index: 31
#2Alies A. van Mullem (EUR: Erasmus University Rotterdam)H-Index: 4
Last. Robin P. Peeters (EUR: Erasmus University Rotterdam)H-Index: 68
view all 4 authors...
Normal thyroid hormone (TH) metabolism and action require adequate cellular TH signalling. This entails proper function of TH transporters in the plasma membrane, intracellular deiodination of TH and action of the bioactive hormone T3 at its nuclear receptors (TRs). The present review summarizes the discoveries of different syndromes with reduced sensitivity at the cellular level. Mutations in the TH transporter MCT8 cause psychomotor retardation and abnormal thyroid parameters. Mutations in the...
#1Logan J. Everett (UPenn: University of Pennsylvania)H-Index: 20
#2Mitchell A. Lazar (UPenn: University of Pennsylvania)H-Index: 145
Nuclear receptors (NRs) encompass a superfamily of transcription factors (TFs), numbering 48 in humans, that bind and respond directly to hormonal, metabolic, developmental, and environmental signals1,2. NRs have proven to be tractable targets in the treatment of a variety of human diseases, ranging from hormone deficiency to diabetes and cancer1,2. Moreover, the NR superfamily provides an excellent paradigm for linking extracellular signals to changes in gene expression1,3. Basic NR structure i...
#1Simon W. Beaven (UCLA: University of California, Los Angeles)H-Index: 16
#2Aleksey V. Matveyenko (UCLA: University of California, Los Angeles)H-Index: 34
Last. Peter Tontonoz (UCLA: University of California, Los Angeles)H-Index: 103
view all 10 authors...
Summary Liver X receptors (LXRs) regulate lipogenesis and inflammation, but their contribution to the metabolic syndrome is unclear. We show that LXRs modulate key aspects of the metabolic syndrome in mice. LXRαβ-deficient- ob/ob (LOKO) mice remain obese but show reduced hepatic steatosis and improved insulin sensitivity compared to ob/ob mice. Impaired hepatic lipogenesis in LOKO mice is accompanied by reciprocal increases in adipose lipid storage, reflecting tissue-selective effects on the SRE...
#1Daniel F. Vatner (Yale University)H-Index: 13
#2Dirk Weismann (Yale University)H-Index: 23
Last. Varman T. Samuel (Yale University)H-Index: 59
view all 14 authors...
Liver-specific thyroid hormone receptor-β (TRβ)-specific agonists are potent lipid-lowering drugs that also hold promise for treating nonalcoholic fatty liver disease and hepatic insulin resistance. We investigated the effect of two TRβ agonists (GC-1 and KB-2115) in high-fat-fed male Sprague-Dawley rats treated for 10 days. GC-1 treatment reduced hepatic triglyceride content by 75%, but the rats developed fasting hyperglycemia and hyperinsulinemia, attributable to increased endogenous glucose p...
#1Neil B. Ruderman (BU: Boston University)H-Index: 111
#2David CarlingH-Index: 94
Last. Jose M. CacicedoH-Index: 19
view all 4 authors...
Insulin resistance (IR) and hyperinsulinemia are hallmarks of the metabolic syndrome, as are central adiposity, dyslipidemia, and a predisposition to type 2 diabetes, atherosclerotic cardiovascular disease, hypertension, and certain cancers. Regular exercise and calorie restriction have long been known to increase insulin sensitivity and decrease the prevalence of these disorders. The subsequent identification of AMP-activated protein kinase (AMPK) and its activation by exercise and fuel depriva...
#1Frédéric Flamant (École normale supérieure de Lyon)H-Index: 34
#2Karine Gauthier (École normale supérieure de Lyon)H-Index: 23
Abstract Background Thyroid hormone receptors TRα1, TRβ1 and TRβ2 are broadly expressed and exert a pleiotropic influence on many developmental and homeostatic processes. Extensive genetic studies in mice precisely defined their respective function. Scope of review The purpose of the review is to discuss two puzzling issues: – The isoform specificity problem: the different functions of TRα1, TRβ1 and TRβ2 might reflect either their different distribution in tissues or differences in the receptor...
#1Miguel López (Ciber)H-Index: 68
#2Clara V. Alvarez (University of Santiago de Compostela)H-Index: 26
Last. Carlos Dieguez (Ciber)H-Index: 121
view all 4 authors...
Classically, medical textbooks taught that most effects of thyroid hormones (THs) on energy homeostasis are directly exerted in peripheral tissues. However, current evidence is changing (and challenging) our perspective about the role of THs from a ‘peripheral' to a ‘central' vision, implying that they affect food intake, energy expenditure, and metabolism by acting, to a large extent, at the central level. Interestingly, effects of THs are interrelated with global energy sensors in the central ...
#1Inna Astapova (BIDMC: Beth Israel Deaconess Medical Center)H-Index: 19
#2Anthony N. Hollenberg (BIDMC: Beth Israel Deaconess Medical Center)H-Index: 60
Abstract Background The thyroid hormone receptor (TR) isoforms interact with a variety of coregulators depending upon the availability of T3 to mediate their transcriptional effect. Classically, in the absence of ligand, the TRs recruit the nuclear corepressors, NCoR and SMRT, to mediate transcriptional repression on positively regulated TR target genes. However, new insight into the roles of NCoR and SMRT using in vivo models have better defined the role of nuclear corepressors both in the abse...
Cited By866
#1Ana Arias-Borrego (University of Huelva)H-Index: 9
#2Inés VelascoH-Index: 3
Last. Tamara García-Barrera (University of Huelva)H-Index: 32
view all 4 authors...
Abstract null null Human breast milk (HBM) has a beneficial impact on health programming, growth and neurodevelopment of newborns. Increase in iodine intake is recommended for pregnant women in order to produce enough thyroid hormones to meet foetal requirements. In this work, a combined analytical multiplatform based on gas chromatography coupled to mass spectrometry and ultra-high performance liquid chromatography coupled to quadrupole-time-of-flight mass spectrometry has been applied in the f...
#1L.A. Vaccaro (UGA: University of Georgia)
#2Tom E. Porter (UMD: University of Maryland, College Park)H-Index: 31
Last. L.E. Ellestad (UGA: University of Georgia)
view all 3 authors...
Commercial selection for meat-type (broiler) chickens has produced economically valuable birds with fast growth rates, enhanced muscle mass, and highly efficient feed utilization. The physiological changes that account for this improvement and unintended consequences associated with them remain largely unexplored, despite their potential to guide further advancements in broiler production efficiency. To identify effects of genetic selection on hormonal signaling in the adrenocorticotropic and th...
#1Anita A. Thambirajah (UVic: University of Victoria)H-Index: 9
#2Michael G. Wade (Health Canada)H-Index: 33
Last. Caren C. Helbing (UVic: University of Victoria)H-Index: 32
view all 0 authors...
Thyroid hormones (THs) are important regulators of growth, development, and homeostasis of all vertebrates. There are many environmental contaminants that are known to disrupt TH action, yet their mechanisms are only partially understood. While the effects of Endocrine Disrupting Chemicals (EDCs) are mostly studied as "hormone system silos", the present critical review highlights the complexity of EDCs interfering with TH function through their interactions with other hormonal axes involved in r...
#1José Luis Martínez-Guitarte (UNED: National University of Distance Education)H-Index: 21
#2Eulalia María Beltrán (CSIC: Spanish National Research Council)H-Index: 8
Last. María Victoria Pablos (CSIC: Spanish National Research Council)H-Index: 8
view all 6 authors...
Abstract null null Reclaimed water (RW) obtained from wastewater treatment plants (WWTP) is used for irrigation, groundwater recharge, among other potential uses. Although most pollutants are removed, traces of them are frequently found, which can affect organisms and alter the environment. The presence of a myriad of contaminants in RW makes it a complex mixture with very diverse effects and interactions. A previous study, in which tadpoles were exposed to RW and RW spiked with Carbamazepine (C...
#1Marek Strączkowski (PAN: Polish Academy of Sciences)H-Index: 12
#2Agnieszka Nikolajuk (PAN: Polish Academy of Sciences)H-Index: 23
Last. Monika Karczewska-Kupczewska (UMB: Medical University of Białystok)H-Index: 20
view all 6 authors...
Background: Thyroid hormone (TH) regulates metabolic pathways which may interfere with insulin action. There is limited knowledge on adipose tissue (AT) and skeletal muscle (SM) expression of genes...
#1Qin Xia (Boston Children's Hospital)
#2Weifeng Qian (Nanjing Medical University)
Last. Jingjing Liu (Soochow University (Suzhou))
view all 11 authors...
Abstract Objective. Graves’ disease (GD) related hyperthyroidism (HT) has profound effects on metabolic activity and metabolism of macromolecules affecting energy homeostasis. In this study, we aimed to get a comprehensive understanding of the metabolic changes and their clinical relevance in GD children. Methods. We investigated serum substances from 30 newly diagnosed GD children and 30 age- and gender-matched healthy controls. We explored the metabolomics using ultra-high-performance liquid c...
#1Hamed Abdollahpour (University of Gilan)H-Index: 3
#2Bahram Falahatkar (University of Gilan)H-Index: 18
Last. Glen Van Der Kraak (U of G: University of Guelph)H-Index: 70
view all 3 authors...
Abstract null null This study examined the effects of thyroxine (T4) on hematological indices, immune parameters and the stress markers of female sterlet sturgeon. Adult broodstock (708 ± 37 g) were assigned to three groups each consisting of ten females. Fish were injected with coconut oil (control), 1 mg T4 kg body weight−1 in coconut oil (T1) or 10 mg T4 kg body weight−1 in coconut oil (T10). Injections were given intraperitoneally four times over a 170-day treatment period. At the end of the...
This website uses cookies.
We use cookies to improve your online experience. By continuing to use our website we assume you agree to the placement of these cookies.
To learn more, you can find in our Privacy Policy.