ArticleDiabetes2014
Tissue-specific inactivation of type 2 deiodinase reveals multilevel control of fatty acid oxidation by thyroid hormone in the mouse.
Article in Diabetes, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 63 citations in OpenAlex.
- Fueling or Fighting Cancer? The Thermogenic Paradox of Brown Adipose Tissue.Current obesity reports · 2026Review
- Association between fatty acid profile and normal thyroid hormone with different glucose status.BMC endocrine disorders · 2026Observational
- Increased Expression of PHGDH Under High-Selenium Stress In Vivo.Biological trace element research · 2024Article
- 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
- Understanding the Roles of Selenium on Thyroid Hormone-Induced Thermogenesis in Adipose Tissue.Biological trace element research · 2024Review
- Understanding the Roles of Selenium on Thyroid Hormone-Induced Thermogenesis in Adipose Tissue.Biological trace element research · 2024Review
- Genetic Background Strongly Influences the Impact of Carrying the Thr92Ala-DIO2 Polymorphism in the Male Mouse.Endocrinology · 2024Article
- Mechanism of action of the bile acid receptor TGR5 in obesity.Acta pharmaceutica Sinica. B · 2024Review
- Tracing links between micronutrients and type 2 diabetes risk: the singular role of selenium.Frontiers in endocrinology · 2024Article
- Endothelial c-Myc knockout disrupts metabolic homeostasis and triggers the development of obesity.Frontiers in cell and developmental biology · 2024Article
- Selenium status and type 2 diabetes risk.Archives of biochemistry and biophysics · 2022Review
- Article
- Deiodinases and the Three Types of Thyroid Hormone Deiodination Reactions.Endocrinology and metabolism (Seoul, Korea) · 2021Review
- Deiodinases and the Metabolic Code for Thyroid Hormone Action.Endocrinology · 2021Review
- Central vs. Peripheral Action of Thyroid Hormone in Adaptive Thermogenesis: A Burning Topic.Cells · 2021Review
- Iodine Deficiency Increases Fat Contribution to Energy Expenditure in Male Mice.Endocrinology · 2020Article
- Thermogenesis in Adipose Tissue Activated by Thyroid Hormone.International journal of molecular sciences · 2020Review
- Mechanisms of insulin resistance related to white, beige, and brown adipocytes.Molecular metabolism · 2020Review
- Tolerance to Selenoprotein Loss Differs between Human and Mouse.Molecular biology and evolution · 2020Article
- Paradigms of Dynamic Control of Thyroid Hormone Signaling.Endocrine reviews · 2019Review
Corrections and comments
- Erratum issuedFerreira, Alexandre [corrected to Ferreira, Alexander R]
Authors and funding
12 authors at 3 institutions in 3 countries.
Funding
Abstract
Type 2 deiodinase (D2) converts the prohormone thyroxine (T4) to the metabolically active molecule 3,5,3'-triiodothyronine (T3), but its global inactivation unexpectedly lowers the respiratory exchange rate (respiratory quotient [RQ]) and decreases food intake. Here we used FloxD2 mice to generate systemically euthyroid fat-specific (FAT), astrocyte-specific (ASTRO), or skeletal-muscle-specific (SKM) D2 knockout (D2KO) mice that were monitored continuously. The ASTRO-D2KO mice also exhibited lower diurnal RQ and greater contribution of fatty acid oxidation to energy expenditure, but no differences in food intake were observed. In contrast, the FAT-D2KO mouse exhibited sustained (24 h) increase in RQ values, increased food intake, tolerance to glucose, and sensitivity to insulin, all supporting greater contribution of carbohydrate oxidation to energy expenditure. Furthermore, FAT-D2KO animals that were kept on a high-fat diet for 8 weeks gained more body weight and fat, indicating impaired brown adipose tissue (BAT) thermogenesis and/or inability to oxidize the fat excess. Acclimatization of FAT-D2KO mice at thermoneutrality dissipated both features of this phenotype. Muscle D2 does not seem to play a significant metabolic role given that SKM-D2KO animals exhibited no phenotype. The present findings are unique in that they were obtained in systemically euthyroid animals, revealing that brain D2 plays a dominant albeit indirect role in fatty acid oxidation via its sympathetic control of BAT activity. D2-generated T3 in BAT accelerates fatty acid oxidation and protects against diet-induced obesity.
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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.