Cited by 2,421Thyroid Disorders and TreatmentsAdipose Tissue and MetabolismRegulation of Appetite and Obesity

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Thyroid Hormone Regulation of Metabolism

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Mullur, Rashmi, Liu, Yan-Yun, Brent, Gregory A.·2014·Physiological Reviews

DOI 10.1152/physrev.00030.2013PMC PMC4044302

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Abstract

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 (T 4 ), to the active form, triiodothyronine (T 3 ), 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.

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Association Between a Novel Variant of the Human Type 2 Deiodinase Gene Thr92Ala and Insulin Resistance
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Regulation of the uncoupling protein gene expression
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Thyroid hormone excess and glucose intolerance
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Background
Brown Fat Activation Mediates Cold-Induced Thermogenesis in Adult Humans in Response to a Mild Decrease in Ambient Temperature
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The role of thyroid hormones in the control of energy expenditure
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Thyroid hormone modulates glucose production via a sympathetic pathway from the hypothalamic paraventricular nucleus to the liver
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The quantitative contributions of mitochondrial proton leak and ATP turnover reactions to the changed respiration rates of hepatocytes from rats of different thyroid status
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Leptin Activates a Novel CNS Mechanism for Insulin-Independent Normalization of Severe Diabetic Hyperglycemia
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Self-citation
Thyroid hormone-related regulation of gene expression in human fatty liver.
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Association of cocaine- and amphetamine-regulated transcript-immunoreactive elements with thyrotropin-releasing hormone-synthesizing neurons in the hypothalamic paraventricular nucleus and its role in the regulation of the hypothalamic-pituitary-thyroid axis during fasting
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Thyroid Hormone Induced Brown Adipose Tissue and Amelioration of Diabetes in a Patient with Extreme Insulin Resistance
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Bile Acids and the Membrane Bile Acid Receptor TGR5—Connecting Nutrition and Metabolism
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Coordination of hypothalamic and pituitary T3 production regulates TSH expression
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Thyroid Hormone Promotes Postnatal Rat Pancreatic β-Cell Development and Glucose-Responsive Insulin Secretion Through MAFA
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Altered relationship between protonmotive force and respiration rate in non‐phosphorylating liver mitochondria isolated from rats of different thyroid hormone status
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Desiccated Thyroid Extract Compared With Levothyroxine in the Treatment of Hypothyroidism: A Randomized, Double-Blind, Crossover Study
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The nuclear corepressor, NCoR, regulates thyroid hormone action in vivo
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Pathophysiological Importance of Thyroid Hormone Transporters
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Activation of phosphatidylinositol 3-kinase signaling by a mutant thyroid hormone β receptor
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Thyroid Hormone and Adipocyte Differentiation
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Reciprocal Regulation of Hepatic and Adipose Lipogenesis by Liver X Receptors in Obesity and Insulin Resistance
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Mild Cold Exposure Modulates Fibroblast Growth Factor 21 (FGF21) Diurnal Rhythm in Humans: Relationship between FGF21 Levels, Lipolysis, and Cold-Induced Thermogenesis
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Thyroid Hormone Regulates Hepatic Expression of Fibroblast Growth Factor 21 in a PPARα-dependent Manner
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Links between Thyroid Hormone Action, Oxidative Metabolism, and Diabetes Risk?
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The Role of the Thyrotropin-Releasing Hormone (TRH) Neuron as a Metabolic Sensor
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Disruption of Thyroid Hormone Activation in Type 2 Deiodinase Knockout Mice Causes Obesity With Glucose Intolerance and Liver Steatosis Only at Thermoneutrality
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DOPAMINE IS A PHYSIOLOGICAL REGULATOR OF THYROTROPHIN (TSH) SECRETION IN NORMAL MAN
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Diiodothyropropionic acid (DITPA) in the treatment of MCT8 deficiency
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“Treatment with diiodothyropropionic acid (DITPA), in animal models and humans with inactivation or mutation in the MCT8 gene, results in reduction in serum TSH and serum T3, and an improvement in hypermetabolism with weight gain and reduced caloric needs (60, 262).”
Background
Endocrine manifestations of eating disorders
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3-Iodothyronamine: a novel hormone controlling the balance between glucose and lipid utilisation
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Prevalence of Thyroid Dysfunction in Patients with Type 2 Diabetes
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Thyroid Hormone Receptor β-Deficient Mice Show Complete Loss of the Normal Cholesterol 7α-Hydroxylase (CYP7A) Response to Thyroid Hormone but Display Enhanced Resistance to Dietary Cholesterol
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Role of the Iodothyronine Deiodinases in the Physiology and Pathophysiology of Thyroid Hormone Action
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Triiodothyronine‐mediated upregulation of UCP2 and UCP3 mRNA expression in human skeletal muscle without coordinated induction of mitochondrial respiratory chain genes
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DITPA (3,5-Diiodothyropropionic Acid), a Thyroid Hormone Analog to Treat Heart Failure: Phase II Trial Veterans Affairs Cooperative Study
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Novel Thyroxine Derivatives, Thyronamine and 3-iodothyronamine, Induce Transient Hypothermia and Marked Neuroprotection Against Stroke Injury
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Mechanism of Thyroid-Hormone Regulated Expression of the SERCA Genes in Skeletal Muscle: Implications for Thermogenesis
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Activation of PPARα lowers synthesis and concentration of cholesterol by reduction of nuclear SREBP-2
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Thyroid hormone receptor-β agonists prevent hepatic steatosis in fat-fed rats but impair insulin sensitivity via discrete pathways
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A Thyroid Hormone Analog with Reduced Dependence on the Monocarboxylate Transporter 8 for Tissue Transport
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Peroxisomal Proliferator-activated Receptor-γ Coactivator-1α (PGC-1α) Enhances the Thyroid Hormone Induction of Carnitine Palmitoyltransferase I (CPT-Iα)
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Clinical Phenotype of a New Type of Thyroid Hormone Resistance Caused by a Mutation of the TRα1 Receptor: Consequences of LT4 Treatment
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Peripheral Metabolism of Thyroid Hormone and Glucose Homeostasis
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Distinct Dysregulation of Lipid Metabolism by Unliganded Thyroid Hormone Receptor Isoforms
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Sterol Regulatory Element-binding Protein-2- and Liver X Receptor-driven Dual Promoter Regulation of Hepatic ABC Transporter A1 Gene Expression
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Weight Loss after Therapy of Hypothyroidism Is Mainly Caused by Excretion of Excess Body Water Associated with Myxoedema
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Ubiquitination-induced conformational change within the deiodinase dimer is a switch regulating enzyme activity
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Mice with a Targeted Deletion of the Type 2 Deiodinase Are Insulin Resistant and Susceptible to Diet Induced Obesity
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Thyroid hormone is required for hypothalamic neurons regulating cardiovascular functions
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Background
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Authors: Mullur, R., Liu, Y.-Y., & Brent, G. A.
Affiliations: University of California, Los Angeles (US)
Corresponding author: Brent, Gregory A.
ORCID: Mullur, Rashmi
Liu, Yan-Yun
Brent, Gregory A.
Venue: Physiological Reviews
Publisher: American Physiological Society
Published: 2014-04
Volume: 94
Issue: 2
Pages: 355-382
ISSN: 0031-9333 (ISSN-L)
1522-1210
DOI: 10.1152/physrev.00030.2013
PMC: PMC4044302
OpenAlex: W1966824338
Cited by: 2,421
References: 292
Citations by year: 2026: 223 · 2025: 273 · 2024: 300 · 2023: 273 · 2022: 269 · 2021: 237 · 2020: 254 · 2019: 163 · 2018: 132 · 2017: 118 · 2016: 90 · 2015: 60 · 2014: 27
FWCI: 15.61
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Physiological Reviews (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Cancer Institute (F32CA090073)
National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK98576, R01DK098576)
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
Keywords: thyroid hormones, thyroid hormone receptor, triiodothyronine, adaptive thermogenesis, brown adipose tissue, hypothalamus, thyrotropin-releasing hormone, thyroid-stimulating hormone, leptin, appetite regulation, adrenergic system, peroxisome proliferator-activated receptors, liver X receptor, bile acid signaling, hepatic insulin sensitivity, hepatic gluconeogenesis, cholesterol metabolism, carbohydrate metabolism, metabolic disorders
MeSH terms: Animals, Body Weight, Cholesterol, Energy Metabolism, Humans, Thyroid Gland, Thyroid Hormones, Triglycerides, Signal Transduction, Thermogenesis, Carbohydrate Metabolism

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Thyroid Hormone Regulation of Metabolism

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