{"id":"89e166f2-38e2-5f43-b1c7-889c880d532f","stable_key":"b26c9d01-98fd-50d3-8f39-44db46961ee5:acetate-no-human-glp1","predicate":"preserves_measured_pool","statement":"Inulin but not resistant starch significantly increased the short-chain fatty acid area under the curve from 4 to 6 hours, yet neither affected the GLP-1 or PYY area under the curve, while ghrelin at 6 hours after inulin was significantly lower than after glucose and the change in short-chain fatty acid area was negatively related to the change in ghrelin area; responses did not differ significantly between lean and overweight subjects.","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"neutral","is_public":true,"mechanism_event_id":"64282c56-e5f1-572d-9be5-2207bec5849e","mechanism_event_label":"In people the fatty acids rose and the two appetite hormones did not move, though ghrelin fell.","subject":{"id":"0f953feb-e5b3-5928-93c4-81c40a83b1cf","slug":"inulin","display_name":"Inulin","entity_type_key":"chemical_species"},"object":{"id":"9086d887-f5ea-5dfb-a68f-adb2c2bda3c7","slug":"plasma-glp1-response","display_name":"Plasma GLP-1 response in the specified meal or glucose challenge","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"64282c56-e5f1-572d-9be5-2207bec5849e","stable_key":"b26c9d01-98fd-50d3-8f39-44db46961ee5:acetate-no-human-glp1-event","event_type":"observed_intervention","label":"In people the fatty acids rose and the two appetite hormones did not move, though ghrelin fell.","description":"Inulin but not resistant starch significantly increased the short-chain fatty acid area under the curve from 4 to 6 hours, yet neither affected the GLP-1 or PYY area under the curve, while ghrelin at 6 hours after inulin was significantly lower than after glucose and the change in short-chain fatty acid area was negatively related to the change in ghrelin area; responses did not differ significantly between lean and overweight subjects.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"73549889-f47c-573b-afa2-c0b79b766218","slug":"plasma-pyy-response","display_name":"PYY secretion measured in plasma or perfusate","entity_type_key":"cellular_process"},"role":"unchanged_measure","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"5087ac12-f71f-5485-ba1f-f5fc9677bf4b","slug":"plasma-ghrelin","display_name":"Plasma ghrelin concentration","entity_type_key":"cellular_process"},"role":"lowered_measure","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"63a35e8c-4622-5780-b65d-e39e83fb19ac","slug":"resistant-starch","display_name":"Resistant starch","entity_type_key":"chemical_species"},"role":"comparator_fibre","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"27ae778c-8456-5ce8-b627-6c4b39d85ffa","slug":"ghrelin","display_name":"Ghrelin","entity_type_key":"peptide"},"role":"lowered_hormone","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"0f953feb-e5b3-5928-93c4-81c40a83b1cf","slug":"inulin","display_name":"Inulin","entity_type_key":"chemical_species"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""},{"entity":{"id":"9086d887-f5ea-5dfb-a68f-adb2c2bda3c7","slug":"plasma-glp1-response","display_name":"Plasma GLP-1 response in the specified meal or glucose challenge","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":5,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/acetate-research/27966574.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"7c0282e2d96baff8a6dde713af91c9df8641d7075c78cf1453ee7d74f6016cd3\", \"start_char\": 0, \"end_char\": 1724, \"text_sha256\": \"7c0282e2d96baff8a6dde713af91c9df8641d7075c78cf1453ee7d74f6016cd3\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Randomised single-blind crossover in 13 overweight or obese and 12 lean humans","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"75 g glucose alone, or with 24 g inulin or 28.2 g resistant starch, with blood sampled over 6 hours","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"The ligand did rise: inulin significantly increased the 4 to 6 hour short-chain fatty acid area under the curve. The authors note that a longer adaptation or a larger sample might give a different answer.","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":"Human","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"In people the fatty acids rose and the two appetite hormones did not move, though ghrelin fell.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[acetate-p27966574] Acute increases in serum colonic short-chain fatty acids elicited by inulin do not increase GLP-1 or PYY responses but may reduce ghrelin in lean and overweight humans. (2017). https://pubmed.ncbi.nlm.nih.gov/27966574/ DOI: 10.1038/ejcn.2016.249","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Whole body","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"345035c6-d4af-5047-a6a8-3beef454c45c","evidence_kind":"source_excerpt","locator":"Lines 368-379","start_line":368,"end_line":379,"excerpt":"### acetate-no-human-glp1\nInulin but not resistant starch significantly increased the short-chain fatty acid area under the curve from 4 to 6 hours, yet neither affected the GLP-1 or PYY area under the curve, while ghrelin at 6 hours after inulin was significantly lower than after glucose and the change in short-chain fatty acid area was negatively related to the change in ghrelin area; responses did not differ significantly between lean and overweight subjects.\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: In people the fatty acids rose and the two appetite hormones did not move, though ghrelin fell.\norganism: Human\ntissue_or_cell_type: Whole body\nexperimental_model: Randomised single-blind crossover in 13 overweight or obese and 12 lean humans\nlimitations: The ligand did rise: inulin significantly increased the 4 to 6 hour short-chain fatty acid area under the curve. The authors note that a longer adaptation or a larger sample might give a different answer.\nexposure: 75 g glucose alone, or with 24 g inulin or 28.2 g resistant starch, with blood sampled over 6 hours\nevidence_span: {\"source_cache\": \"artifacts/acetate-research/27966574.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"7c0282e2d96baff8a6dde713af91c9df8641d7075c78cf1453ee7d74f6016cd3\", \"start_char\": 0, \"end_char\": 1724, \"text_sha256\": \"7c0282e2d96baff8a6dde713af91c9df8641d7075c78cf1453ee7d74f6016cd3\"}\n[acetate-p27966574] Acute increases in serum colonic short-chain fatty acids elicited by inulin do not increase GLP-1 or PYY responses but may reduce ghrelin in lean and overweight humans. (2017). https://pubmed.ncbi.nlm.nih.gov/27966574/ DOI: 10.1038/ejcn.2016.249","model_system":"Randomised single-blind crossover in 13 overweight or obese and 12 lean humans","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [acetate-p27966574] Acute increases in serum colonic short-chain fatty acids elicited by inulin do not increase GLP-1 or PYY responses but may reduce ghrelin in lean and overweight humans. (2017). https://pubmed.ncbi.nlm.nih.gov/27966574/ DOI: 10.1038/ejcn.2016.249","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":[{"id":"57958831-4d7d-5309-a2c8-6bb2fce79d5f","title":"Do short-chain fatty acids raise GLP-1 and PYY, and if so is the receptor involved?","kind":"contradiction","status":"open","why":"Three designs disagree on two separate points. Knockout work in rats and mice found that propionate stimulates GLP-1 and PYY and that deleting FFA2 abolishes the response, placing the effect on the receptor. The isolated perfused rat colon found the opposite pattern: acetate and butyrate released GLP-1 but propionate did not, a receptor-specific synthetic agonist had no effect at all, a receptor antagonist did not block the response, and inhibitors of ATP synthesis abolished it, so those authors concluded the fatty acids act as colonocyte fuel rather than as ligands. A randomised crossover in 25 lean and overweight humans raised serum short-chain fatty acids with inulin and found no change in either hormone, though ghrelin fell. The designs differ in species, in which fatty acid was given, in route, and in whether the tissue was intact and perfused. Receptor pharmacology in the perfused study also found the natural fatty acids to be low-potency partial agonists, around 750-fold weaker than a synthetic full agonist, which bears on whether physiological concentrations could act through the receptor at all. Neither the species question nor the mechanism question is resolved here.","resolution":"Unresolved; needs review.","created_at":"2026-09-22 01:55:55","record_type":"conflict","display_label":"Recorded conflict","record_url":"/conflicts/57958831-4d7d-5309-a2c8-6bb2fce79d5f","sides":[{"conflict_id":"57958831-4d7d-5309-a2c8-6bb2fce79d5f","ordinal":0,"label":"In rodents the receptor is what releases the two gut hormones; delete it and the response goes.","revision_id":"9bfeb605-f589-5e99-84b9-e56968a3bc1f","start_line":316,"end_line":327,"quote":"### acetate-scfa-glp1-rodent\nPropionate stimulated secretion of both peptide YY and GLP-1 from wild-type murine colonic crypt cultures and this effect was significantly attenuated in cultures from FFA2 knockout mice, while intra-colonic infusion of propionate elevated both hormones in portal vein plasma in rats and mice but did not significantly stimulate their release in FFA2 knockout mice.\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: In rodents the receptor is what releases the two gut hormones; delete it and the response goes.\norganism: Rat and mouse\ntissue_or_cell_type: Colon\nexperimental_model: Wistar rats, C57BL6 mice and FFA2 knockout mice, with colonic crypt cultures and portal vein sampling\nlimitations: Establishes the receptor-to-hormone step in rodents using propionate rather than acetate. The knockout is the strength of the design.\nexposure: Propionate applied to colonic crypt cultures and infused into the colon, with FFA2 deletion as the test of mediation\nevidence_span: {\"source_cache\": \"artifacts/acetate-research/25109781.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"c3c934644f9308be7b2c26f969858debd0d1dbf19bee7e307e529d392fe135d6\", \"start_char\": 0, \"end_char\": 1621, \"text_sha256\": \"c3c934644f9308be7b2c26f969858debd0d1dbf19bee7e307e529d392fe135d6\"}\n[acetate-p25109781] The short chain fatty acid propionate stimulates GLP-1 and PYY secretion via free fatty acid receptor 2 in rodents. (2015). https://pubmed.ncbi.nlm.nih.gov/25109781/ DOI: 10.1038/ijo.2014.153","source_key":"import-b26c9d01-98fd-50d3-8f39-44db46961ee5","source_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)","claim_ids":["bb1616a5-6773-5948-a18c-32de252fd202"]},{"conflict_id":"57958831-4d7d-5309-a2c8-6bb2fce79d5f","ordinal":1,"label":"Blocking the receptors changed nothing, while blocking energy production abolished the response.","revision_id":"9bfeb605-f589-5e99-84b9-e56968a3bc1f","start_line":342,"end_line":353,"quote":"### acetate-receptor-not-required\nA FFAR2- and FFAR3-specific agonist had no effect on colonic GLP-1 output and a FFAR3 antagonist did not decrease the short-chain fatty acid-induced GLP-1 response, whereas the calcium channel blocker nifedipine, the KATP-channel opener diazoxide and the ATP synthesis inhibitor 2,4-dinitrophenol completely abolished the responses, leading the authors to conclude that the fatty acids are metabolised and function as a colonocyte energy source rather than acting through the receptors.\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: Blocking the receptors changed nothing, while blocking energy production abolished the response.\norganism: Rat\ntissue_or_cell_type: Colon\nexperimental_model: Isolated perfused rat colon with luminal and vascular short-chain fatty acid infusion and receptor pharmacology\nlimitations: An isolated organ preparation with an intact blood supply. It reaches the opposite mechanistic conclusion from the knockout work in this collection and is why the receptor route is recorded as disputed.\nexposure: Acetate, propionate and butyrate perfused luminally or vascularly, with FFAR2/FFAR3 agonists, an FFAR3 antagonist, nifedipine, diazoxide and 2,4-dinitrophenol\nevidence_span: {\"source_cache\": \"artifacts/acetate-research/29494208.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"9f8def7b832fdd5d5aed67891c84b18b597d558d9361a92412ccc44264b88126\", \"start_char\": 0, \"end_char\": 2445, \"text_sha256\": \"9f8def7b832fdd5d5aed67891c84b18b597d558d9361a92412ccc44264b88126\"}\n[acetate-p29494208] The impact of short-chain fatty acids on GLP-1 and PYY secretion from the isolated perfused rat colon. (2018). https://pubmed.ncbi.nlm.nih.gov/29494208/ DOI: 10.1152/ajpgi.00346.2017","source_key":"import-b26c9d01-98fd-50d3-8f39-44db46961ee5","source_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)","claim_ids":["4afb6318-93e2-5e67-b47e-e8896eec9968"]},{"conflict_id":"57958831-4d7d-5309-a2c8-6bb2fce79d5f","ordinal":2,"label":"In people the fatty acids rose and the two appetite hormones did not move, though ghrelin fell.","revision_id":"9bfeb605-f589-5e99-84b9-e56968a3bc1f","start_line":368,"end_line":379,"quote":"### acetate-no-human-glp1\nInulin but not resistant starch significantly increased the short-chain fatty acid area under the curve from 4 to 6 hours, yet neither affected the GLP-1 or PYY area under the curve, while ghrelin at 6 hours after inulin was significantly lower than after glucose and the change in short-chain fatty acid area was negatively related to the change in ghrelin area; responses did not differ significantly between lean and overweight subjects.\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: In people the fatty acids rose and the two appetite hormones did not move, though ghrelin fell.\norganism: Human\ntissue_or_cell_type: Whole body\nexperimental_model: Randomised single-blind crossover in 13 overweight or obese and 12 lean humans\nlimitations: The ligand did rise: inulin significantly increased the 4 to 6 hour short-chain fatty acid area under the curve. The authors note that a longer adaptation or a larger sample might give a different answer.\nexposure: 75 g glucose alone, or with 24 g inulin or 28.2 g resistant starch, with blood sampled over 6 hours\nevidence_span: {\"source_cache\": \"artifacts/acetate-research/27966574.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"7c0282e2d96baff8a6dde713af91c9df8641d7075c78cf1453ee7d74f6016cd3\", \"start_char\": 0, \"end_char\": 1724, \"text_sha256\": \"7c0282e2d96baff8a6dde713af91c9df8641d7075c78cf1453ee7d74f6016cd3\"}\n[acetate-p27966574] Acute increases in serum colonic short-chain fatty acids elicited by inulin do not increase GLP-1 or PYY responses but may reduce ghrelin in lean and overweight humans. (2017). https://pubmed.ncbi.nlm.nih.gov/27966574/ DOI: 10.1038/ejcn.2016.249","source_key":"import-b26c9d01-98fd-50d3-8f39-44db46961ee5","source_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)","claim_ids":["89e166f2-38e2-5f43-b1c7-889c880d532f"]}]}],"corrections":[],"research":null}