{"id":"856592a7-c06a-52f5-92e1-d2b0d4cd336d","stable_key":"6cdb37aa-8998-5ea8-829d-4f995caf98fc:l-carnitine-macrophage-cpt-loss","predicate":"loss_did_not_block","statement":"Genetic loss of Cpt1a or Cpt2 did not reproduce the strong block of IL-4-driven macrophage polarization caused by high-dose etomoxir.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"neutral","is_public":true,"mechanism_event_id":"6c31463f-8142-5a7e-9dd2-550848c182a9","mechanism_event_label":"A drug effect did not prove that the carnitine shuttle was required.","subject":{"id":"6252720d-2cf5-5daa-bc8d-3a53cea6ffb4","slug":"mouse-cpt2","display_name":"Mouse carnitine palmitoyltransferase 2 / Cpt2","entity_type_key":"protein"},"object":{"id":"aab0c8d6-e9ec-5345-8640-80d2ae447c9d","slug":"mouse-macrophage-il4-polarization","display_name":"Mouse macrophage IL-4-induced polarization","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"6c31463f-8142-5a7e-9dd2-550848c182a9","stable_key":"6cdb37aa-8998-5ea8-829d-4f995caf98fc:l-carnitine-macrophage-cpt-loss-event","event_type":"observed_relationship","label":"A drug effect did not prove that the carnitine shuttle was required.","description":"Genetic loss of Cpt1a or Cpt2 did not reproduce the strong block of IL-4-driven macrophage polarization caused by high-dose etomoxir.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"6252720d-2cf5-5daa-bc8d-3a53cea6ffb4","slug":"mouse-cpt2","display_name":"Mouse carnitine palmitoyltransferase 2 / Cpt2","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"aab0c8d6-e9ec-5345-8640-80d2ae447c9d","slug":"mouse-macrophage-il4-polarization","display_name":"Mouse macrophage IL-4-induced polarization","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"785e7874-0c3f-5a3c-b5e8-ffad2861cf5f","slug":"mouse-cpt1a","display_name":"Mouse carnitine palmitoyltransferase 1A / Cpt1a","entity_type_key":"protein"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"2414d192-9440-54eb-8ed9-d7fecd6552d7","slug":"etomoxir","display_name":"Etomoxir","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"6e34c035-9371-578f-b799-fd2a14e9e40f","slug":"l-carnitine","display_name":"L-Carnitine","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary abstract and full-text mouse macrophage methods","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Mouse macrophage genetic and pharmacologic comparisons.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Context-specific immune result, not a statement that fatty-acid oxidation never matters.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"l-carnitine","display_name":"L-Carnitine","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"A drug effect did not prove that the carnitine shuttle was required.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Etomoxir Inhibits Macrophage Polarization by Disrupting CoA Homeostasis. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30043752/ · DOI 10.1016/j.cmet.2018.06.001","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"3f7692fb-1a46-5479-b217-af4ff0731bc1","evidence_kind":"source_excerpt","locator":"Lines 442-448","start_line":442,"end_line":448,"excerpt":"## l-carnitine-macrophage-cpt-loss\nA drug effect did not prove that the carnitine shuttle was required.\nGenetic loss of Cpt1a or Cpt2 did not reproduce the strong block of IL-4-driven macrophage polarization caused by high-dose etomoxir.\nModel: Mouse macrophage genetic and pharmacologic comparisons.\nLimitations: Context-specific immune result, not a statement that fatty-acid oxidation never matters.\nEvidence access: Primary abstract and full-text mouse macrophage methods\nEtomoxir Inhibits Macrophage Polarization by Disrupting CoA Homeostasis. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30043752/ · DOI 10.1016/j.cmet.2018.06.001","model_system":"Mouse macrophage genetic and pharmacologic comparisons.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Original curation paraphrase; 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