{"id":"d8a7ff22-9e8e-566e-92c1-4debce6f75ad","stable_key":"c8c7aa13-14c6-5f5c-9afc-9217d0f2f736:hfcs-copper-liver","predicate":"worsens_under_low_copper","statement":"The combination of marginal copper deficiency and fructose feeding increased hepatic triglyceride and liver injury in rats.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"07bab35b-0420-5528-8202-ba5820ce2eb3","mechanism_event_label":"The combination of marginal copper deficiency and fructose feeding increased hepatic triglyceride and liver injury in rats.","subject":{"id":"3c379840-5688-5b5d-84c0-5950b4fd8f17","slug":"fructose","display_name":"Fructose","entity_type_key":"small_molecule"},"object":{"id":"e1856ab7-5c9b-59f1-8a99-5a20966ef466","slug":"rat-hepatic-triglyceride-content","display_name":"Rat hepatic triglyceride content","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"07bab35b-0420-5528-8202-ba5820ce2eb3","stable_key":"c8c7aa13-14c6-5f5c-9afc-9217d0f2f736:hfcs-copper-liver-event","event_type":"observed_relationship","label":"The combination of marginal copper deficiency and fructose feeding increased hepatic triglyceride and liver injury in rats.","description":"The combination of marginal copper deficiency and fructose feeding increased hepatic triglyceride and liver injury in rats.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"3c379840-5688-5b5d-84c0-5950b4fd8f17","slug":"fructose","display_name":"Fructose","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"e1856ab7-5c9b-59f1-8a99-5a20966ef466","slug":"rat-hepatic-triglyceride-content","display_name":"Rat hepatic triglyceride content","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"9f0afdde-1ec1-5c8a-bb5e-f3b2b75f67f6","slug":"copper","display_name":"Copper","entity_type_key":"nutrient_element"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"nutrient_deficiency","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"dose","value_text":"Dietary copper 6 or 1.6 mg/kg diet; water with or without 30% w/v fructose","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"duration","value_text":"4 weeks","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_access","value_text":"Primary full-text methods/results and metadata inspected.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_scope","value_text":"literature_reviewed; source-specific curation","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Male weanling Sprague-Dawley rats","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure_scope","value_text":"Isolated fructose with copper restriction","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"High-fructose component experiment. Copper concentrations refer to diet, not body weight. Ctr1 expression is not direct copper flux, and human HFCS-induced copper deficiency is not established.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"HFCS chapter: actual formulation studies, component biochemistry and interventions are explicitly distinguished.","comparator":null,"unit":null,"notes":"","entity":{"slug":"high-fructose-corn-syrup","display_name":"High-Fructose Corn Syrup / HFCS","entity_type_key":"chemical_species"}},{"dimension":"organism","value_text":"Male weanling Sprague-Dawley rats","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"The combination of marginal copper deficiency and fructose feeding increased hepatic triglyceride and liver injury in rats.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"High fructose feeding induces copper deficiency in Sprague-Dawley rats: a novel mechanism for obesity related fatty liver. (2012). https://pubmed.ncbi.nlm.nih.gov/21781943/ DOI: 10.1016/j.jhep.2011.05.030","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"route","value_text":"Oral diet and drinking water","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue","value_text":"Copper status, duodenum and hepatic triglyceride","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"nutrient_deficiency","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"1d0444a1-3fbc-54c2-8e69-20972fbeef74","evidence_kind":"source_excerpt","locator":"Lines 521-531","start_line":521,"end_line":531,"excerpt":"## hfcs-copper-liver\nThe combination of marginal copper deficiency and fructose feeding increased hepatic triglyceride and liver injury in rats.\nModel/species: Male weanling Sprague-Dawley rats\nTissue: Copper status, duodenum and hepatic triglyceride\nExposure: Dietary copper 6 or 1.6 mg/kg diet; water with or without 30% w/v fructose\nRoute: Oral diet and drinking water\nDuration: 4 weeks\nExposure scope: Isolated fructose with copper restriction\nLimits: High-fructose component experiment. Copper concentrations refer to diet, not body weight. Ctr1 expression is not direct copper flux, and human HFCS-induced copper deficiency is not established.\nReference: High fructose feeding induces copper deficiency in Sprague-Dawley rats: a novel mechanism for obesity related fatty liver. (2012). https://pubmed.ncbi.nlm.nih.gov/21781943/ DOI: 10.1016/j.jhep.2011.05.030\nAccess: Primary full-text methods/results and metadata inspected.","model_system":"Male weanling Sprague-Dawley rats","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Exact original curation span, not a publisher quotation; provenance retained.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"e863ddf6-7c1e-5a70-8335-7f3ac3eeee92","stable_key":"import-c8c7aa13-14c6-5f5c-9afc-9217d0f2f736","title":"High-Fructose Corn Syrup: mechanism of action and metabolic impact (2026-09-20)","document_type":"imported_text","citation_label":"Original AI-assisted curation of twenty primary studies and official FDA composition information, with one reused canonical glucose-transport claim. Study-specific citations, negative findings and limitations retained. Not publisher full text.","file_path":"","sha256":"f4721923a83b368d549ba110a4f8c8738026210b32f6d29f3bd3200aa420f3b3","revision_id":"45827d73-cb6d-5aff-969b-af364b74b168","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}