{"id":"42ae6f9e-530c-5eab-b9eb-b7e735fdab85","stable_key":"b26c9d01-98fd-50d3-8f39-44db46961ee5:acetate-sodium-acetate-hepatocyte","predicate":"activates","statement":"Sodium acetate, in the form of neutralised acetic acid, directly activated AMPK and lowered the expression of genes such as glucose-6-phosphatase and sterol regulatory element binding protein 1 in rat hepatocytes, leading the authors to conclude that the hypoglycaemic effect might be due to activation of AMPK in the liver.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"5b2f28db-ea56-55fc-8438-881cfab7ed9f","mechanism_event_label":"The neutralised salt switched on the liver cell energy sensor directly.","subject":{"id":"e366e758-1fb0-5573-aed1-34f6df874ac7","slug":"acetate","display_name":"Acetate","entity_type_key":"small_molecule"},"object":{"id":"8128eec0-61cc-51ef-8d4e-5ec9678e8dfa","slug":"ampk-complexes","display_name":"AMP-activated protein kinase complexes","entity_type_key":"protein_family"},"evidence_count":1,"mechanism_event":{"id":"5b2f28db-ea56-55fc-8438-881cfab7ed9f","stable_key":"b26c9d01-98fd-50d3-8f39-44db46961ee5:acetate-sodium-acetate-hepatocyte-event","event_type":"biochemical_relationship","label":"The neutralised salt switched on the liver cell energy sensor directly.","description":"Sodium acetate, in the form of neutralised acetic acid, directly activated AMPK and lowered the expression of genes such as glucose-6-phosphatase and sterol regulatory element binding protein 1 in rat hepatocytes, leading the authors to conclude that the hypoglycaemic effect might be due to activation of AMPK in the liver.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"ff6ccfc3-22e6-55e0-8e4e-9951aca6b3fa","slug":"rat-hepatocyte","display_name":"Rat hepatocyte","entity_type_key":"cell_type"},"role":"test_system","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"4965f9ab-be2e-594a-9ede-aac0335f6107","slug":"g6pc","display_name":"Glucose-6-phosphatase","entity_type_key":"protein"},"role":"suppressed_gene","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"278d2aa8-ed70-58ab-8650-3d9b32f725b5","slug":"srebf1","display_name":"Sterol regulatory element-binding protein 1 / SREBP-1","entity_type_key":"protein"},"role":"suppressed_factor","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"c7480cb4-3fb7-53d0-9224-9638d26658b4","slug":"neutralised-vinegar","display_name":"Vinegar neutralised to pH 6.0 with sodium bicarbonate, supplying sodium acetate","entity_type_key":"chemical_species"},"role":"corresponding_dietary_form","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"e366e758-1fb0-5573-aed1-34f6df874ac7","slug":"acetate","display_name":"Acetate","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""},{"entity":{"id":"8128eec0-61cc-51ef-8d4e-5ec9678e8dfa","slug":"ampk-complexes","display_name":"AMP-activated protein kinase complexes","entity_type_key":"protein_family"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":5,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/acetate-research/16630552.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"8e99fe94e17c850602d0da9607212293dfc8d773e356b73ef37c4b071bbeabea\", \"start_char\": 0, \"end_char\": 914, \"text_sha256\": \"8e99fe94e17c850602d0da9607212293dfc8d773e356b73ef37c4b071bbeabea\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"KK-Ay diabetic mice fed for 8 weeks, with rat hepatocyte experiments","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"0.3% dietary acetic acid for 8 weeks; sodium acetate as neutralised acetic acid applied to rat hepatocytes","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"The hepatocyte arm used the neutralised salt and still activated AMPK, which does not sit easily beside the human finding that the acid rather than the salt lowered glucose. Both are recorded.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Acetic acid research collection; topical membership is not evidence of a direct clinical effect, and the ingested acid is recorded separately from the circulating acetate anion.","comparator":null,"unit":null,"notes":"","entity":{"slug":"acetic-acid","display_name":"Acetic acid","entity_type_key":"chemical_species"}},{"dimension":"organism","value_text":"Mouse and rat cells","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"The neutralised salt switched on the liver cell energy sensor directly.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[acetate-p16630552] Acetic acid activates hepatic AMPK and reduces hyperglycemia in diabetic KK-A(y) mice. (2006). https://pubmed.ncbi.nlm.nih.gov/16630552/ DOI: 10.1016/j.bbrc.2006.03.176","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Liver","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"ed63ce59-c61c-5928-88d2-6f9baded3f63","evidence_kind":"source_excerpt","locator":"Lines 420-431","start_line":420,"end_line":431,"excerpt":"### acetate-sodium-acetate-hepatocyte\nSodium acetate, in the form of neutralised acetic acid, directly activated AMPK and lowered the expression of genes such as glucose-6-phosphatase and sterol regulatory element binding protein 1 in rat hepatocytes, leading the authors to conclude that the hypoglycaemic effect might be due to activation of AMPK in the liver.\nCondition category: normal\nnutrient_topic: Acetic acid research collection; topical membership is not evidence of a direct clinical effect, and the ingested acid is recorded separately from the circulating acetate anion.\nplain_language: The neutralised salt switched on the liver cell energy sensor directly.\norganism: Mouse and rat cells\ntissue_or_cell_type: Liver\nexperimental_model: KK-Ay diabetic mice fed for 8 weeks, with rat hepatocyte experiments\nlimitations: The hepatocyte arm used the neutralised salt and still activated AMPK, which does not sit easily beside the human finding that the acid rather than the salt lowered glucose. Both are recorded.\nexposure: 0.3% dietary acetic acid for 8 weeks; sodium acetate as neutralised acetic acid applied to rat hepatocytes\nevidence_span: {\"source_cache\": \"artifacts/acetate-research/16630552.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"8e99fe94e17c850602d0da9607212293dfc8d773e356b73ef37c4b071bbeabea\", \"start_char\": 0, \"end_char\": 914, \"text_sha256\": \"8e99fe94e17c850602d0da9607212293dfc8d773e356b73ef37c4b071bbeabea\"}\n[acetate-p16630552] Acetic acid activates hepatic AMPK and reduces hyperglycemia in diabetic KK-A(y) mice. (2006). https://pubmed.ncbi.nlm.nih.gov/16630552/ DOI: 10.1016/j.bbrc.2006.03.176","model_system":"KK-Ay diabetic mice fed for 8 weeks, with rat hepatocyte experiments","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [acetate-p16630552] Acetic acid activates hepatic AMPK and reduces hyperglycemia in diabetic KK-A(y) mice. (2006). https://pubmed.ncbi.nlm.nih.gov/16630552/ DOI: 10.1016/j.bbrc.2006.03.176","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"8356baaf-173c-5549-80cd-bbbb2007ffb5","stable_key":"import-b26c9d01-98fd-50d3-8f39-44db46961ee5","title":"Acetic acid: the ingested acid, the receptors acetate binds, the acetyl-CoA it becomes, and the acetyl groups that reach histones (2026-09-21)","document_type":"imported_text","citation_label":"AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text.","file_path":"","sha256":"1441d249b16db25c0d488407e5cc881222acffc2f16af88cb3197d9d5697bccc","revision_id":"9bfeb605-f589-5e99-84b9-e56968a3bc1f","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}