{"id":"3a48b874-3996-5b3d-bf76-ce34a8b7454e","stable_key":"475ea55a-65e9-51c3-a539-738a6a8f683f:mangiferin-lkb1-acc","predicate":"blocks_response","statement":"LKB1 knockdown prevented the norathyriol-associated increase in ACC phosphorylation.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"4c7cf978-e15b-544b-b56d-d53f5e5c36eb","mechanism_event_label":"Removing an upstream component interrupted the response.","subject":{"id":"ad407d5a-2d5d-5ecf-80c8-44c460ac2f15","slug":"human-stk11-knockdown","display_name":"Experimental human STK11 / LKB1 siRNA knockdown","entity_type_key":"protein_state"},"object":{"id":"f1623f3f-bba0-5289-b1b7-214fb0504a76","slug":"human-acc-assay-family","display_name":"Human acetyl-CoA carboxylase activity, isoform unresolved in assay","entity_type_key":"protein_family"},"evidence_count":1,"mechanism_event":{"id":"4c7cf978-e15b-544b-b56d-d53f5e5c36eb","stable_key":"475ea55a-65e9-51c3-a539-738a6a8f683f:mangiferin-lkb1-acc-event","event_type":"biochemical_relationship","label":"Removing an upstream component interrupted the response.","description":"LKB1 knockdown prevented the norathyriol-associated increase in ACC phosphorylation.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"d0f7f42a-ac45-5144-9ea5-a7586896cc6e","slug":"norathyriol","display_name":"Norathyriol","entity_type_key":"small_molecule"},"role":"intervention","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"718da13a-06a0-58c2-ab52-900ab07f9bf3","slug":"stk11","display_name":"Human liver kinase B1 / STK11","entity_type_key":"protein"},"role":"affected_machinery","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"ad407d5a-2d5d-5ecf-80c8-44c460ac2f15","slug":"human-stk11-knockdown","display_name":"Experimental human STK11 / LKB1 siRNA knockdown","entity_type_key":"protein_state"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"f1623f3f-bba0-5289-b1b7-214fb0504a76","slug":"human-acc-assay-family","display_name":"Human acetyl-CoA carboxylase activity, isoform unresolved in assay","entity_type_key":"protein_family"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/mangiferin-research/29563875.fulltext.txt\", \"locator\": \"Primary full-text span; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"1a48a1f92d67cd91638969bb1ec3cb9f18cb3cb4e29c7e5f2bacf627dda76415\", \"start_char\": 33073, \"end_char\": 35334, \"text_sha256\": \"166efaa83fd229a3e036a60bf4e23173a7b50a3044686fe1a324d6dc604354a9\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"KK-Ay mouse liver experiments and mechanistic HepG2 studies","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Norathyriol in sodium-oleate lipid-loading model; micromolar range","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Phosphorylation and expression are scoped to experiments; no established human fatty-liver therapy or direct SIRT1 ligand claim.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Mangiferin research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"mangiferin","display_name":"Mangiferin","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Homo sapiens for HepG2 experiments; mouse findings separately scoped","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Removing an upstream component interrupted the response.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[mangiferin-p29563875] Mangiferin Improves Hepatic Lipid Metabolism Mainly Through Its Metabolite-Norathyriol by Modulating SIRT-1/AMPK/SREBP-1c Signaling. 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