{"id":"b3c187b9-39fe-546f-8a32-ee93e6829ea8","stable_key":"e3f6ce02-0bd7-5103-acc1-68503ab6751b:hcc-crat-independent","predicate":"increases_in_recorded_comparison","statement":"ALCAR still increased histone acetylation when ACLY and Crat were absent and ACSS2 was inhibited.","claim_class":"observational","status":"source_recorded","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"d4cea504-4821-5d43-ad11-7078070da32f","mechanism_event_label":"ALCAR still increased histone acetylation when ACLY and Crat were absent and ACSS2 was inhibited.","subject":{"id":"5ce394a9-6ec6-56dd-866f-37d85c0556e4","slug":"acetylcarnitine","display_name":"Acetyl-L-carnitine","entity_type_key":"small_molecule"},"object":{"id":"c5a36cde-28a1-5d3a-8384-d115c27db067","slug":"mouse-hcc-histone-acetylation","display_name":"Mouse HCC-cell histone acetylation","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"d4cea504-4821-5d43-ad11-7078070da32f","stable_key":"e3f6ce02-0bd7-5103-acc1-68503ab6751b:hcc-crat-independent-event","event_type":"experimental_observation","label":"ALCAR still increased histone acetylation when ACLY and Crat were absent and ACSS2 was inhibited.","description":"### hcc-crat-independent\n\nALCAR still increased histone acetylation when ACLY and Crat were absent and ACSS2 was inhibited.\nACSS2 inhibition slightly suppressed the response but did not abolish it. This is a bypass in a perturbed cancer-cell model, not proof that all ALCAR use bypasses these enzymes.\nModel and exposure: Mouse HCC cells; ACLY/CrAT knockout plus ACSS2 inhibitor; Fig. 7F and supplementary S8I.\nLimitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.\nReference: Acetylcarnitine shuttling links mitochondrial metabolism to histone acetylation and lipogenesis. | 2023 | https://pubmed.ncbi.nlm.nih.gov/37134161/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC10156126/ | https://doi.org/10.1126/sciadv.adf0115 | Access: Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"5ce394a9-6ec6-56dd-866f-37d85c0556e4","slug":"acetylcarnitine","display_name":"Acetyl-L-carnitine","entity_type_key":"small_molecule"},"role":"tested factor","stoichiometry":null,"state_label":"ALCAR in ACLY/CrAT-deficient cells with ACSS2 inhibition","sequence_order":0,"notes":""},{"entity":{"id":"c5a36cde-28a1-5d3a-8384-d115c27db067","slug":"mouse-hcc-histone-acetylation","display_name":"Mouse HCC-cell histone acetylation","entity_type_key":"cellular_process"},"role":"measured outcome","stoichiometry":null,"state_label":"increase","sequence_order":1,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_condition","value_text":"supplied","comparator":"Matched perturbed cells without ALCAR","unit":null,"notes":"Condition belongs to the full experimental contrast; do not separate a joint intervention.","entity":{"slug":"acetylcarnitine","display_name":"Acetyl-L-carnitine","entity_type_key":"small_molecule"}},{"dimension":"experimental_condition","value_text":"deleted","comparator":"Matched perturbed cells without ALCAR","unit":null,"notes":"Condition belongs to the full experimental contrast; do not separate a joint intervention.","entity":{"slug":"mouse-acly","display_name":"Mouse ATP-citrate lyase / Acly","entity_type_key":"protein"}},{"dimension":"experimental_condition","value_text":"inhibited","comparator":"Matched perturbed cells without ALCAR","unit":null,"notes":"Condition belongs to the full experimental contrast; do not separate a joint intervention.","entity":{"slug":"mouse-acss2","display_name":"Mouse acyl-CoA synthetase short-chain family member 2 / Acss2","entity_type_key":"protein"}},{"dimension":"experimental_condition","value_text":"deleted","comparator":"Matched perturbed cells without ALCAR","unit":null,"notes":"Condition belongs to the full experimental contrast; do not separate a joint intervention.","entity":{"slug":"mouse-crat","display_name":"Mouse carnitine acetyltransferase / Crat","entity_type_key":"protein"}},{"dimension":"experimental_contrast","value_text":"{\"intervention\": \"ALCAR in ACLY/CrAT-deficient cells with ACSS2 inhibition\", \"comparator\": \"Matched perturbed cells without ALCAR\", \"endpoint\": \"ALCAR still increased histone acetylation when ACLY and Crat were absent and ACSS2 was inhibited.\", \"effect_direction\": \"increase\", \"combination\": \"joint\", \"conditions\": [{\"entity_slug\": \"acetylcarnitine\", \"state\": \"supplied\"}, {\"entity_slug\": \"mouse-acly\", \"state\": \"deleted\"}, {\"entity_slug\": \"mouse-crat\", \"state\": \"deleted\"}, {\"entity_slug\": \"mouse-acss2\", \"state\": \"inhibited\"}]}","comparator":null,"unit":null,"notes":"Explicit extracted experimental comparison; source-derived draft.","entity":null},{"dimension":"experimental_model","value_text":"Mouse HCC cells; ACLY/CrAT knockout plus ACSS2 inhibitor; Fig. 7F and supplementary S8I.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"interpretation_status","value_text":"Source-derived curation with stated access limits; ungraded, not independent replication.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Acetyl-L-carnitine collection; exact intervention and molecular form govern interpretation.","comparator":null,"unit":null,"notes":"","entity":{"slug":"acetylcarnitine","display_name":"Acetyl-L-carnitine","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"ALCAR still increased histone acetylation when ACLY and Crat were absent and ACSS2 was inhibited.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Acetylcarnitine shuttling links mitochondrial metabolism to histone acetylation and lipogenesis. | https://pubmed.ncbi.nlm.nih.gov/37134161/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC10156126/ | https://doi.org/10.1126/sciadv.adf0115","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"source_locator","value_text":"Reviewed reference hcc-crat-independent; ACSS2 inhibition slightly suppressed the response but did not abolish it. This is a bypass in a perturbed cancer-cell model, not proof that all ALCAR use bypasses these enzymes.","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"ced749ce-6d77-51b4-ae69-48f5b524c28a","evidence_kind":"source_excerpt","locator":"Lines 252-258","start_line":252,"end_line":258,"excerpt":"### hcc-crat-independent\n\nALCAR still increased histone acetylation when ACLY and Crat were absent and ACSS2 was inhibited.\nACSS2 inhibition slightly suppressed the response but did not abolish it. This is a bypass in a perturbed cancer-cell model, not proof that all ALCAR use bypasses these enzymes.\nModel and exposure: Mouse HCC cells; ACLY/CrAT knockout plus ACSS2 inhibitor; Fig. 7F and supplementary S8I.\nLimitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.\nReference: Acetylcarnitine shuttling links mitochondrial metabolism to histone acetylation and lipogenesis. | 2023 | https://pubmed.ncbi.nlm.nih.gov/37134161/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC10156126/ | https://doi.org/10.1126/sciadv.adf0115 | Access: Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.","model_system":"Mouse HCC cells; ACLY/CrAT knockout plus ACSS2 inhibitor; Fig. 7F and supplementary S8I.","directness":"reported_statement","verification_status":"source_recorded","notes":"Original paraphrase in the retained reviewed reference, not a verbatim primary-paper quotation. Access level is explicit.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"2588f904-245a-597a-8a12-65118013fb90","stable_key":"import-e3f6ce02-0bd7-5103-acc1-68503ab6751b","title":"Acetyl-L-carnitine: detailed mechanisms of action (reviewed 6 October 2026)","document_type":"imported_text","citation_label":"AI-assisted original review of primary studies and clearly identified official records. Exact primary access is stated; no independent replication is claimed.","file_path":"","sha256":"84cc82d6fbb0fd5d73c4ce779e9f88e7f0184ba2d29b18ad0f153815380f2975","revision_id":"dac7a950-dbe5-5c7a-9c70-2ea711d5c71a","review_status":"source_recorded","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}