Component

DIO2

Independent protein record for Iodothyronine deiodinase 2.

8 recorded relationships. Experimental role, claim status and evidence remain attached to each record.

Read recorded mechanisms Open recursive mind map

How nutrients influence it

Every nutrient with a recorded effect on this component, credited to the nutrient that acted rather than the chapter that recorded it. Open a nutrient to see the findings and the conditions they were measured under.

How nutrients reach it in more than one step

Chains of two or more recorded steps that end here, grouped by the nutrient they start from. Each step is a separate finding, so a chain is a route a mechanism could take, not proof that it does.

Tracing routes…

What it does

Every recorded relationship this component is part of, grouped by its role. Plain wording comes first; the technical statement follows.

Recorded relationships

What it acts on

  1. Cloning and characterization of human DIO2 cDNA identified DIO2 as a selenoprotein.

    DIO2 → Protein-incorporated selenocysteine residue source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    Selenium-containing DIO2 metabolizes iodine-containing T4.
    evidence_locator
    Primary abstract
    evidence_spans
    [{"source_document": "artifacts/iodine-metabolism-sources/8755651.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1406}]
    experimental_model
    Rat and human DIO2 cDNA cloning and characterization
    exposure
    DIO2 sequence and functional characterization; no nutritional intervention.
    limitations
    Protein composition does not establish a dietary threshold, benefit from extra selenium, or species-independent regulation.
    nutrient_topic
    Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
    organism
    Human DIO2; study also characterized rat orthologue
    plain_language
    The T4-activating enzyme contains selenium as part of its protein structure.
    primary_references
    [i-met-8755651] Cloning of the mammalian type II iodothyronine deiodinase. A selenoprotein differentially expressed and regulated in human and rat brain and other tissues. (1996). https://pubmed.ncbi.nlm.nih.gov/8755651/ DOI: 10.1172/jci118806
    tissue_or_cell_type
    Human cDNA and expression characterization

    Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 1114–1127

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rat and human DIO2 cDNA cloning and characterization · source_derived_draft · unverified_draft

    ### i-met-human-dio2-selenoprotein Cloning and characterization of human DIO2 cDNA identified DIO2 as a selenoprotein. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The T4-activating enzyme contains selenium as part of its protein structure. organism: Human DIO2; study also characterized rat orthologue tissue_or_cell_type: Human cDNA and expression characterization experimental_model: Rat and human DIO2 cDNA cloning and characterization limitations: Protein composition does not establish a dietary threshold, benefit from extra selenium, or species-independent regulation. exposure: DIO2 sequence and functional characterization; no nutritional intervention. cross_nutrient: Selenium-containing DIO2 metabolizes iodine-containing T4. evidence_locator: Primary abstract evidence_spans: [{"source_document": "artifacts/iodine-metabolism-sources/8755651.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1406}] [i-met-8755651] Cloning of the mammalian type II iodothyronine deiodinase. A selenoprotein differentially expressed and regulated in human and rat brain and other tissues. (1996). https://pubmed.ncbi.nlm.nih.gov/8755651/ DOI: 10.1172/jci118806
    Complete structured claim and evidence

  2. Type 2 iodothyronine deiodinase is a selenoenzyme, the product of the cAMP-dependent Dio2 gene, which increases 10- to 50-fold during cold stress only in brown adipose tissue.

    DIO2 → T3 source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/cold-research/11696583.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "adbd82ff8c43d8a2718cfa752c9a0607c367648d6573b968eb885c883376dc68", "start_char": 0, "end_char": 1332, "text_sha256": "adbd82ff8c43d8a2718cfa752c9a0607c367648d6573b968eb885c883376dc68"}
    experimental_model
    Mice with targeted disruption of the Dio2 gene, with brown adipocyte assays and T3 rescue
    exposure
    Cold stress, with norepinephrine, CL316,243 or forskolin stimulation, and a single T3 injection
    limitations
    The selenoenzyme is the link between thyroid hormone and sympathetic signalling. Plasma T3 was normal in the knockouts, so the defect is local hormone generation, not circulating hormone.
    nutrient_topic
    Cold water immersion research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Cold water immersion
    organism
    Mouse
    plain_language
    Cold makes brown fat build a selenium enzyme that manufactures active thyroid hormone on the spot.
    primary_references
    [cold-p11696583] The type 2 iodothyronine deiodinase is essential for adaptive thermogenesis in brown adipose tissue. (2001). https://pubmed.ncbi.nlm.nih.gov/11696583/ DOI: 10.1172/jci13803
    tissue_or_cell_type
    Brown adipose tissue

    Cold water immersion: cold sensing, heat production, the catecholamine axis and what repeated exposure changes (2026-09-19) · lines 377–388

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mice with targeted disruption of the Dio2 gene, with brown adipocyte assays and T3 rescue · source_derived_draft · unverified_draft

    ### cold-dio2-selenoenzyme Type 2 iodothyronine deiodinase is a selenoenzyme, the product of the cAMP-dependent Dio2 gene, which increases 10- to 50-fold during cold stress only in brown adipose tissue. Condition category: normal nutrient_topic: Cold water immersion research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: Cold makes brown fat build a selenium enzyme that manufactures active thyroid hormone on the spot. organism: Mouse tissue_or_cell_type: Brown adipose tissue experimental_model: Mice with targeted disruption of the Dio2 gene, with brown adipocyte assays and T3 rescue limitations: The selenoenzyme is the link between thyroid hormone and sympathetic signalling. Plasma T3 was normal in the knockouts, so the defect is local hormone generation, not circulating hormone. exposure: Cold stress, with norepinephrine, CL316,243 or forskolin stimulation, and a single T3 injection evidence_span: {"source_cache": "artifacts/cold-research/11696583.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "adbd82ff8c43d8a2718cfa752c9a0607c367648d6573b968eb885c883376dc68", "start_char": 0, "end_char": 1332, "text_sha256": "adbd82ff8c43d8a2718cfa752c9a0607c367648d6573b968eb885c883376dc68"} [cold-p11696583] The type 2 iodothyronine deiodinase is essential for adaptive thermogenesis in brown adipose tissue. (2001). https://pubmed.ncbi.nlm.nih.gov/11696583/ DOI: 10.1172/jci13803
    Complete structured claim and evidence

  3. DIO2 catalyzes outer-ring deiodination of T4 to T3 in functional enzyme-expression experiments.

    DIO2 → T3 source_derived_draftliterature_reviewed:direct_experimental
    Experimental context and source evidence
    experimental_model
    Rat and human DIO2 cDNA characterization and functional expression.
    limitations
    This reaction alone cannot diagnose hidden tissue hypothyroidism from normal blood tests or quantify benefit from selenium intake.
    organism
    Human and rat

    Selenium: literature corrections and mechanism additions · lines 1009–1018

    Metabolic Ledger literature curation, 17 September 2026; primary papers linked individually · supports · Rat and human DIO2 cDNA characterization and functional expression. · secondary_verified · secondary_verified

    ## dio2-t4-to-t3 DIO2 converts T4 into the active thyroid hormone T3. DIO2 catalyzes outer-ring deiodination of T4 to T3 in functional enzyme-expression experiments. Experimental model: Rat and human DIO2 cDNA characterization and functional expression. Organism: Human and rat Limitations: This reaction alone cannot diagnose hidden tissue hypothyroidism from normal blood tests or quantify benefit from selenium intake. Primary reference: [Cloning of the mammalian type II iodothyronine deiodinase](https://www.jci.org/articles/view/118806)
    Complete structured claim and evidence

What acts on it

  1. Fibroblasts from affected siblings with a recessive SECISBP2 defect had reduced DIO2 activity; linkage did not map the defect to DIO2 itself.

    Patients with recessive SECISBP2 defects → DIO2 source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    cross_nutrient
    Selenium-incorporation machinery is required for hormone-processing selenoproteins; this is not dietary selenium deficiency.
    evidence_locator
    Primary abstract
    evidence_spans
    [{"source_document": "artifacts/iodine-metabolism-sources/16228000.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1084}]
    experimental_model
    Two human families with recessive SECISBP2 variants; patient fibroblast enzyme assays and linkage analysis
    exposure
    Inherited SECISBP2 variants; no dietary deprivation exposure.
    limitations
    Abstract-only; variant-specific kinetics and dietary rescue were not established.
    nutrient_topic
    Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
    organism
    Homo sapiens
    plain_language
    A defect in selenium-incorporation machinery can impair thyroid-hormone processing even when the deiodinase gene is not the cause.
    primary_references
    [i-met-16228000] Mutations in SECISBP2 result in abnormal thyroid hormone metabolism. (2005). https://pubmed.ncbi.nlm.nih.gov/16228000/ DOI: 10.1038/ng1654
    tissue_or_cell_type
    Patient fibroblasts
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 1099–1112

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Two human families with recessive SECISBP2 variants; patient fibroblast enzyme assays and linkage analysis · source_derived_draft · unverified_draft

    ### i-met-secisbp2-fibroblast-dio2 Fibroblasts from affected siblings with a recessive SECISBP2 defect had reduced DIO2 activity; linkage did not map the defect to DIO2 itself. Condition category: machinery_impairment nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: A defect in selenium-incorporation machinery can impair thyroid-hormone processing even when the deiodinase gene is not the cause. organism: Homo sapiens tissue_or_cell_type: Patient fibroblasts experimental_model: Two human families with recessive SECISBP2 variants; patient fibroblast enzyme assays and linkage analysis limitations: Abstract-only; variant-specific kinetics and dietary rescue were not established. exposure: Inherited SECISBP2 variants; no dietary deprivation exposure. cross_nutrient: Selenium-incorporation machinery is required for hormone-processing selenoproteins; this is not dietary selenium deficiency. evidence_locator: Primary abstract evidence_spans: [{"source_document": "artifacts/iodine-metabolism-sources/16228000.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1084}] [i-met-16228000] Mutations in SECISBP2 result in abnormal thyroid hormone metabolism. (2005). https://pubmed.ncbi.nlm.nih.gov/16228000/ DOI: 10.1038/ng1654
    Complete structured claim and evidence

  2. WSB1 knockdown in HEK293 cells increased steady-state D2 approximately fivefold and prolonged its half-life two- to threefold.

    Human WSB1 → DIO2 source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_locator
    Figure 2D-G; Methods: Constructs and Transfections
    evidence_spans
    [{"source_document": "artifacts/iodine-metabolism-sources/15965468.txt", "locator": "Figure 2D-G; Methods: Constructs and Transfections", "start_char": 14434, "end_char": 15884}]
    experimental_model
    HEK293 knockdown, recombinant mouse Wsb1/human DIO2 expression and ubiquitination assays; separate chicken explant experiments
    exposure
    WSB1 RNA interference; activity assays used FLAG-D2, western analyses used FLAG-CysD2; turnover experiments included cycloheximide.
    limitations
    Wild-type and Sec-to-Cys experimental constructs have different roles; no diet was manipulated.
    nutrient_topic
    Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
    organism
    Human HEK293; mouse Wsb1 used in complementation arms
    plain_language
    Reducing the enzyme-removal machinery allows more DIO2 to remain available.
    primary_references
    [i-met-15965468] The Hedgehog-inducible ubiquitin ligase subunit WSB-1 modulates thyroid hormone activation and PTHrP secretion in the developing growth plate. (2005). https://pubmed.ncbi.nlm.nih.gov/15965468/ DOI: 10.1038/ncb1272
    tissue_or_cell_type
    Transfected HEK293 cells
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 1158–1170

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · HEK293 knockdown, recombinant mouse Wsb1/human DIO2 expression and ubiquitination assays; separate chicken explant experiments · source_derived_draft · unverified_draft

    ### i-met-wsb1-knockdown-dio2 WSB1 knockdown in HEK293 cells increased steady-state D2 approximately fivefold and prolonged its half-life two- to threefold. Condition category: machinery_impairment nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Reducing the enzyme-removal machinery allows more DIO2 to remain available. organism: Human HEK293; mouse Wsb1 used in complementation arms tissue_or_cell_type: Transfected HEK293 cells experimental_model: HEK293 knockdown, recombinant mouse Wsb1/human DIO2 expression and ubiquitination assays; separate chicken explant experiments limitations: Wild-type and Sec-to-Cys experimental constructs have different roles; no diet was manipulated. exposure: WSB1 RNA interference; activity assays used FLAG-D2, western analyses used FLAG-CysD2; turnover experiments included cycloheximide. evidence_locator: Figure 2D-G; Methods: Constructs and Transfections evidence_spans: [{"source_document": "artifacts/iodine-metabolism-sources/15965468.txt", "locator": "Figure 2D-G; Methods: Constructs and Transfections", "start_char": 14434, "end_char": 15884}] [i-met-15965468] The Hedgehog-inducible ubiquitin ligase subunit WSB-1 modulates thyroid hormone activation and PTHrP secretion in the developing growth plate. (2005). https://pubmed.ncbi.nlm.nih.gov/15965468/ DOI: 10.1038/ncb1272
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. Recombinant mouse Wsb1 supported ubiquitination of human DIO2 constructs in a reconstituted assay; disruption of the Wsb1 BC box prevented this effect.

    Mouse Wsb1 → DIO2 ubiquitination source_derived_draftungraded
    Experimental context and source evidence
    evidence_locator
    Figure 1E-F; Methods: Constructs and ubiquitination assay
    evidence_spans
    [{"source_document": "artifacts/iodine-metabolism-sources/15965468.txt", "locator": "Figure 1E-F; Methods: Constructs and ubiquitination assay", "start_char": 13661, "end_char": 14961}]
    experimental_model
    HEK293 knockdown, recombinant mouse Wsb1/human DIO2 expression and ubiquitination assays; separate chicken explant experiments
    exposure
    Mouse Wsb1 versus BC-box mutant M1; assay contained 30 micromolar ubiquitin and 10 micromolar ubiquitin aldehyde.
    limitations
    Paper uses both wild-type FLAG-D2 and Sec133C/Sec266C constructs; this record concerns ubiquitination machinery, not dietary selenium dependence.
    nutrient_topic
    Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
    organism
    Mouse Wsb1 with human DIO2 constructs; cell-free expression system
    plain_language
    An ubiquitin ligase component marks DIO2 for regulation.
    primary_references
    [i-met-15965468] The Hedgehog-inducible ubiquitin ligase subunit WSB-1 modulates thyroid hormone activation and PTHrP secretion in the developing growth plate. (2005). https://pubmed.ncbi.nlm.nih.gov/15965468/ DOI: 10.1038/ncb1272
    tissue_or_cell_type
    Reconstituted ubiquitination assay

    Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 1144–1156

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · HEK293 knockdown, recombinant mouse Wsb1/human DIO2 expression and ubiquitination assays; separate chicken explant experiments · source_derived_draft · unverified_draft

    ### i-met-wsb1-dio2-ubiquitination Recombinant mouse Wsb1 supported ubiquitination of human DIO2 constructs in a reconstituted assay; disruption of the Wsb1 BC box prevented this effect. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: An ubiquitin ligase component marks DIO2 for regulation. organism: Mouse Wsb1 with human DIO2 constructs; cell-free expression system tissue_or_cell_type: Reconstituted ubiquitination assay experimental_model: HEK293 knockdown, recombinant mouse Wsb1/human DIO2 expression and ubiquitination assays; separate chicken explant experiments limitations: Paper uses both wild-type FLAG-D2 and Sec133C/Sec266C constructs; this record concerns ubiquitination machinery, not dietary selenium dependence. exposure: Mouse Wsb1 versus BC-box mutant M1; assay contained 30 micromolar ubiquitin and 10 micromolar ubiquitin aldehyde. evidence_locator: Figure 1E-F; Methods: Constructs and ubiquitination assay evidence_spans: [{"source_document": "artifacts/iodine-metabolism-sources/15965468.txt", "locator": "Figure 1E-F; Methods: Constructs and ubiquitination assay", "start_char": 13661, "end_char": 14961}] [i-met-15965468] The Hedgehog-inducible ubiquitin ligase subunit WSB-1 modulates thyroid hormone activation and PTHrP secretion in the developing growth plate. (2005). https://pubmed.ncbi.nlm.nih.gov/15965468/ DOI: 10.1038/ncb1272
    Complete structured claim and evidence

  2. Cold-exposed Dio2-disrupted mice became hypothermic due to impaired brown adipose thermogenesis despite normal plasma T3 and normal basal UCP1, and survived by compensatory shivering with acute weight loss.

    Experimental Dio2-disrupted mouse genotype → Brown adipose tissue thermogenesis source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    nutrient_deficiency Imported condition classification; unverified.
    evidence_span
    {"source_cache": "artifacts/cold-research/11696583.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "adbd82ff8c43d8a2718cfa752c9a0607c367648d6573b968eb885c883376dc68", "start_char": 0, "end_char": 1332, "text_sha256": "adbd82ff8c43d8a2718cfa752c9a0607c367648d6573b968eb885c883376dc68"}
    experimental_model
    Mice with targeted disruption of the Dio2 gene, with brown adipocyte assays and T3 rescue
    exposure
    Cold stress, with norepinephrine, CL316,243 or forskolin stimulation, and a single T3 injection
    limitations
    The selenoenzyme is the link between thyroid hormone and sympathetic signalling. Plasma T3 was normal in the knockouts, so the defect is local hormone generation, not circulating hormone.
    nutrient_topic
    Cold water immersion research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Cold water immersion
    organism
    Mouse
    plain_language
    Normal hormone in the blood was not enough; the tissue had to make its own.
    primary_references
    [cold-p11696583] The type 2 iodothyronine deiodinase is essential for adaptive thermogenesis in brown adipose tissue. (2001). https://pubmed.ncbi.nlm.nih.gov/11696583/ DOI: 10.1172/jci13803
    tissue_or_cell_type
    Brown adipose tissue
    trigger_kind
    nutrient_deficiency Imported condition classification; unverified.

    Cold water immersion: cold sensing, heat production, the catecholamine axis and what repeated exposure changes (2026-09-19) · lines 390–401

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mice with targeted disruption of the Dio2 gene, with brown adipocyte assays and T3 rescue · source_derived_draft · unverified_draft

    ### cold-dio2-null-hypothermia Cold-exposed Dio2-disrupted mice became hypothermic due to impaired brown adipose thermogenesis despite normal plasma T3 and normal basal UCP1, and survived by compensatory shivering with acute weight loss. Condition category: nutrient_deficiency nutrient_topic: Cold water immersion research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: Normal hormone in the blood was not enough; the tissue had to make its own. organism: Mouse tissue_or_cell_type: Brown adipose tissue experimental_model: Mice with targeted disruption of the Dio2 gene, with brown adipocyte assays and T3 rescue limitations: The selenoenzyme is the link between thyroid hormone and sympathetic signalling. Plasma T3 was normal in the knockouts, so the defect is local hormone generation, not circulating hormone. exposure: Cold stress, with norepinephrine, CL316,243 or forskolin stimulation, and a single T3 injection evidence_span: {"source_cache": "artifacts/cold-research/11696583.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "adbd82ff8c43d8a2718cfa752c9a0607c367648d6573b968eb885c883376dc68", "start_char": 0, "end_char": 1332, "text_sha256": "adbd82ff8c43d8a2718cfa752c9a0607c367648d6573b968eb885c883376dc68"} [cold-p11696583] The type 2 iodothyronine deiodinase is essential for adaptive thermogenesis in brown adipose tissue. (2001). https://pubmed.ncbi.nlm.nih.gov/11696583/ DOI: 10.1172/jci13803
    Complete structured claim and evidence

  3. The authors propose that intracellularly generated T3 is required to saturate thyroid hormone receptor alpha, which has an approximately fourfold lower T3-binding affinity than receptor beta, making the deiodinase an essential component of the thyroid-sympathetic synergism required for thermal homeostasis.

    T3 → Brown adipose tissue thermogenesis source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/cold-research/11696583.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "adbd82ff8c43d8a2718cfa752c9a0607c367648d6573b968eb885c883376dc68", "start_char": 0, "end_char": 1332, "text_sha256": "adbd82ff8c43d8a2718cfa752c9a0607c367648d6573b968eb885c883376dc68"}
    experimental_model
    Mice with targeted disruption of the Dio2 gene, with brown adipocyte assays and T3 rescue
    exposure
    Cold stress, with norepinephrine, CL316,243 or forskolin stimulation, and a single T3 injection
    limitations
    The selenoenzyme is the link between thyroid hormone and sympathetic signalling. Plasma T3 was normal in the knockouts, so the defect is local hormone generation, not circulating hormone.
    nutrient_topic
    Cold water immersion research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Cold water immersion
    organism
    Mouse
    plain_language
    Two receptors need different amounts of hormone, and only local production reaches the hungrier one.
    primary_references
    [cold-p11696583] The type 2 iodothyronine deiodinase is essential for adaptive thermogenesis in brown adipose tissue. (2001). https://pubmed.ncbi.nlm.nih.gov/11696583/ DOI: 10.1172/jci13803
    tissue_or_cell_type
    Brown adipose tissue

    Cold water immersion: cold sensing, heat production, the catecholamine axis and what repeated exposure changes (2026-09-19) · lines 416–427

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mice with targeted disruption of the Dio2 gene, with brown adipocyte assays and T3 rescue · source_derived_draft · unverified_draft

    ### cold-dio2-thyroid-sympathetic-synergy The authors propose that intracellularly generated T3 is required to saturate thyroid hormone receptor alpha, which has an approximately fourfold lower T3-binding affinity than receptor beta, making the deiodinase an essential component of the thyroid-sympathetic synergism required for thermal homeostasis. Condition category: normal nutrient_topic: Cold water immersion research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: Two receptors need different amounts of hormone, and only local production reaches the hungrier one. organism: Mouse tissue_or_cell_type: Brown adipose tissue experimental_model: Mice with targeted disruption of the Dio2 gene, with brown adipocyte assays and T3 rescue limitations: The selenoenzyme is the link between thyroid hormone and sympathetic signalling. Plasma T3 was normal in the knockouts, so the defect is local hormone generation, not circulating hormone. exposure: Cold stress, with norepinephrine, CL316,243 or forskolin stimulation, and a single T3 injection evidence_span: {"source_cache": "artifacts/cold-research/11696583.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "adbd82ff8c43d8a2718cfa752c9a0607c367648d6573b968eb885c883376dc68", "start_char": 0, "end_char": 1332, "text_sha256": "adbd82ff8c43d8a2718cfa752c9a0607c367648d6573b968eb885c883376dc68"} [cold-p11696583] The type 2 iodothyronine deiodinase is essential for adaptive thermogenesis in brown adipose tissue. (2001). https://pubmed.ncbi.nlm.nih.gov/11696583/ DOI: 10.1172/jci13803
    Complete structured claim and evidence

In the sources

Preserved passages that mention this component, quoted exactly. Open one to read it in context.

    This is a research prototype built from draft material. It is not medical advice, and its statements still await verification against the original studies.

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