{"id":"98c18744-15c6-5685-96b0-037d3cde0477","stable_key":"b3c3f45a-50fb-5b79-98d7-5e5228df00db:cold-irisin-shivering","predicate":"increases","statement":"Cold exposure increased circulating irisin and FGF21, with irisin secretion induced in proportion to shivering intensity and of similar magnitude to exercise-stimulated secretion.","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"13c04d53-961e-554b-bae1-5869fa7e1f11","mechanism_event_label":"Shivering muscle releases the same messenger exercising muscle does, in proportion to how hard it shivers.","subject":{"id":"4d0ab5e4-8743-5a7c-8692-57e6d096c4e9","slug":"shivering","display_name":"Shivering thermogenesis","entity_type_key":"cellular_process"},"object":{"id":"e551ddbd-fcb6-50b7-89ef-3e267cc5c84f","slug":"circulating-irisin","display_name":"Circulating irisin concentration","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"13c04d53-961e-554b-bae1-5869fa7e1f11","stable_key":"b3c3f45a-50fb-5b79-98d7-5e5228df00db:cold-irisin-shivering-event","event_type":"observed_intervention","label":"Shivering muscle releases the same messenger exercising muscle does, in proportion to how hard it shivers.","description":"Cold exposure increased circulating irisin and FGF21, with irisin secretion induced in proportion to shivering intensity and of similar magnitude to exercise-stimulated secretion.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"b0ffa3c4-f6cb-5fd1-a251-bb576d6d6a24","slug":"irisin","display_name":"Irisin","entity_type_key":"peptide"},"role":"released_peptide","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"cd4ff64a-aba5-5292-9607-abf68527d5ba","slug":"fndc5","display_name":"Fibronectin type III domain-containing protein 5 / FNDC5","entity_type_key":"protein"},"role":"precursor_protein","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"f711f2f5-9403-55a8-9899-538aacea63ec","slug":"circulating-fgf21","display_name":"Circulating FGF21 concentration","entity_type_key":"cellular_process"},"role":"co_induced_factor","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"4d0ab5e4-8743-5a7c-8692-57e6d096c4e9","slug":"shivering","display_name":"Shivering thermogenesis","entity_type_key":"cellular_process"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"e551ddbd-fcb6-50b7-89ef-3e267cc5c84f","slug":"circulating-irisin","display_name":"Circulating irisin concentration","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/cold-research/24506871.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"980c2630ed13bf2a55f813a6df483edb68a1d6370c0f1afdfcbc7df7817eb610\", \"start_char\": 0, \"end_char\": 1149, \"text_sha256\": \"980c2630ed13bf2a55f813a6df483edb68a1d6370c0f1afdfcbc7df7817eb610\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human cold exposure with circulating myokine measurement and human adipocyte treatment","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Cold exposure sufficient to induce shivering; FNDC5 and FGF21 treatment of human adipocytes","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"The proportionality to shivering intensity is the mechanistic link. Depot-specific adipocyte responses mean this is not a uniform browning effect.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Cold water immersion research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake.","comparator":null,"unit":null,"notes":"","entity":{"slug":"cold-water-immersion","display_name":"Cold water immersion","entity_type_key":"drug"}},{"dimension":"organism","value_text":"Human","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Shivering muscle releases the same messenger exercising muscle does, in proportion to how hard it shivers.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[cold-p24506871] Irisin and FGF21 are cold-induced endocrine activators of brown fat function in humans. (2014). https://pubmed.ncbi.nlm.nih.gov/24506871/ DOI: 10.1016/j.cmet.2013.12.017","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Skeletal muscle and adipose tissue","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"bbe3a2d3-76b7-5886-b5d5-ccf4f3d80409","evidence_kind":"source_excerpt","locator":"Lines 481-492","start_line":481,"end_line":492,"excerpt":"### cold-irisin-shivering\nCold exposure increased circulating irisin and FGF21, with irisin secretion induced in proportion to shivering intensity and of similar magnitude to exercise-stimulated secretion.\nCondition category: normal\nnutrient_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.\nplain_language: Shivering muscle releases the same messenger exercising muscle does, in proportion to how hard it shivers.\norganism: Human\ntissue_or_cell_type: Skeletal muscle and adipose tissue\nexperimental_model: Human cold exposure with circulating myokine measurement and human adipocyte treatment\nlimitations: The proportionality to shivering intensity is the mechanistic link. Depot-specific adipocyte responses mean this is not a uniform browning effect.\nexposure: Cold exposure sufficient to induce shivering; FNDC5 and FGF21 treatment of human adipocytes\nevidence_span: {\"source_cache\": \"artifacts/cold-research/24506871.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"980c2630ed13bf2a55f813a6df483edb68a1d6370c0f1afdfcbc7df7817eb610\", \"start_char\": 0, \"end_char\": 1149, \"text_sha256\": \"980c2630ed13bf2a55f813a6df483edb68a1d6370c0f1afdfcbc7df7817eb610\"}\n[cold-p24506871] Irisin and FGF21 are cold-induced endocrine activators of brown fat function in humans. (2014). https://pubmed.ncbi.nlm.nih.gov/24506871/ DOI: 10.1016/j.cmet.2013.12.017","model_system":"Human cold exposure with circulating myokine measurement and human adipocyte treatment","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [cold-p24506871] Irisin and FGF21 are cold-induced endocrine activators of brown fat function in humans. (2014). https://pubmed.ncbi.nlm.nih.gov/24506871/ DOI: 10.1016/j.cmet.2013.12.017","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"feeccadc-1392-573e-a0b5-0939ee5de6e2","stable_key":"import-b3c3f45a-50fb-5b79-98d7-5e5228df00db","title":"Cold water immersion: cold sensing, heat production, the catecholamine axis and what repeated exposure changes (2026-09-19)","document_type":"imported_text","citation_label":"AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. 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