ArticleEndocrinology2011
Type-2 iodothyronine 5'deiodinase (D2) in skeletal muscle of C57Bl/6 mice. II. Evidence for a role of D2 in the hypermetabolism of thyroid hormone receptor alpha-deficient mice.
Article in Endocrinology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 35 citations in OpenAlex.
- Neural correlates of free T3 alteration after catecholamine depletion in subjects with remitted major depressive disorder and in controls.Psychopharmacology · 2014Trial
- Global loss of selenocysteine lyase in mice drives lipid accumulation in brown adipocytes.American journal of physiology. Endocrinology and metabolism · 2026Article
- Thyroid hormones and metabolic flexibility: tissue-specific control of energy homeostasis.Frontiers in physiology · 2026Review
- The key roles of thyroid hormone in mitochondrial regulation, at interface of human health and disease.Journal of basic and clinical physiology and pharmacology · 2024Review
- Thyroid Hormone Biomonitoring: A Review on Their Metabolism and Machine-Learning Based Analysis on Effects of Endocrine Disrupting Chemicals.Environment & health (Washington, D.C.) · 2024Review
- Pharmacological modulation of adaptive thermogenesis: new clues for obesity management?Journal of endocrinological investigation · 2023Review
- Selenium and selenoproteins in thermogenic adipocytes.Archives of biochemistry and biophysics · 2022Review
- The Role of Thyroid Hormones on Skeletal Muscle Thermogenesis.Metabolites · 2022Review
- Deiodinases and the Metabolic Code for Thyroid Hormone Action.Endocrinology · 2021Review
- Effect of Thyroid Hormones on Adipose Tissue Flexibility.European thyroid journal · 2021Review
- Bile Acids as a New Type of Steroid Hormones Regulating Nonspecific Energy Expenditure of the Body (Review).Sovremennye tekhnologii v meditsine · 2021Review
- Paradigms of Dynamic Control of Thyroid Hormone Signaling.Endocrine reviews · 2019Review
- A Global Loss of Dio2 Leads to Unexpected Changes in Function and Fiber Types of Slow Skeletal Muscle in Male Mice.Endocrinology · 2019Article
- Metabolic Effects of the Intracellular Regulation of Thyroid Hormone: Old Players, New Concepts.Frontiers in endocrinology · 2018Review
- Levothyroxine enhances glucose clearance and blunts the onset of experimental type 1 diabetes mellitus in mice.British journal of pharmacology · 2017Article
- Thyroid hormone activation by type 2 deiodinase mediates exercise-induced peroxisome proliferator-activated receptor-γ coactivator-1α expression in skeletal muscle.The Journal of physiology · 2016Article
- The brain and brown fat.Annals of medicine · 2015Review
- Thyroid hormones and skeletal muscle--new insights and potential implications.Nature reviews. Endocrinology · 2014Review
- The deiodinases and the control of intracellular thyroid hormone signaling during cellular differentiation.Biochimica et biophysica acta · 2013Review
- Role of the type 2 iodothyronine deiodinase (D2) in the control of thyroid hormone signaling.Biochimica et biophysica acta · 2013Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Mice with ablation of the Thra gene have cold intolerance due to an as yet undefined defect in the activation of brown adipose tissue (BAT) uncoupling protein (UCP). They develop an alternate form of facultative thermogenesis, activated at temperatures below thermoneutrality and associated with hypermetabolism and reduced sensitivity to diet-induced obesity. A consistent finding in Thra-0/0 mice is increased type-2 iodothyronine deiodinase (D2) mRNA in skeletal muscle and other tissues. With an improved assay to measure D2 activity, we show here that this enzyme activity is increased in proportion to the mRNA and as a function of the ambient cold. The activation is mediated by the sympathetic nervous system in Thra-0/0, as it is in wild-type genotype mice, but the sympathetic nervous system effect is greater in Thra-0/0 mice. Using D2-ablated mice (Dio2-/-), we reported elsewhere and show here that, in spite of sharing a severe deficiency in BAT thermogenesis with Thra-0/0 and UCP1-knockout mice, they do not have an increase in oxygen consumption, and they gain more weight than wild-type controls when fed a high-fat diet. UCP3 mRNA is highly responsive to thyroid hormone, and it is increased in Thra-0/0 mice, particularly when fed high-fat diets. We show here that muscle UCP3 mRNA in hypothyroid Thra-0/0 mice is responsive to small dose-short regimens of T(4), indicating a role for locally, D2-generated T(3). Lastly, we show that bile acids stimulate not only BAT but also muscle D2 activity, and this is associated with stimulation of muscle UCP3 mRNA expression provided T(4) is present. These observations strongly support the concept that enhanced D2 activity in Thra-0/0 plays a critical role in their alternate form of facultative thermogenesis, stimulating increased fat oxidation by increasing local T(3) generation in skeletal muscle.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.