Component

Human hydroxycarboxylic acid receptor 2 / HCAR2

Human hydroxycarboxylic acid receptor 2 / HCAR2. The model and exposure of each linked claim define its scope.

6 recorded relationships. Experimental role, claim status and evidence remain attached to each record.

Read recorded mechanisms Open recursive mind map

How nutrients influence it

Every nutrient with a recorded effect on this component, credited to the nutrient that acted rather than the chapter that recorded it. Open a nutrient to see the findings and the conditions they were measured under.

How nutrients reach it in more than one step

Chains of two or more recorded steps that end here, grouped by the nutrient they start from. Each step is a separate finding, so a chain is a route a mechanism could take, not proof that it does.

Tracing routes…

What it does

Every recorded relationship this component is part of, grouped by its role. Plain wording comes first; the technical statement follows.

Recorded relationships

What it acts on

  1. Restoring GPR109A expression in human colon cancer cells enabled apoptosis in the presence of butyrate or nicotinate; the receptor-mediated response did not require histone deacetylation inhibition.

    Human hydroxycarboxylic acid receptor 2 / HCAR2 → Apoptosis in human colon cancer cells with restored HCAR2 source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary abstract
    experimental_model
    Human colon cancer-cell receptor reexpression.
    limitations
    An engineered culture rescue does not show that oral supplements restore silenced receptors in patients.
    nutrient_topic
    Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
    plain_language
    Restoring the receptor enabled a response distinct from the HDAC pathway.
    primary_references
    GPR109A is a G-protein-coupled receptor for the bacterial fermentation product butyrate and functions as a tumor suppressor in colon. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19276343/ · DOI 10.1158/0008-5472.CAN-08-4466
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 358–364

    AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human colon cancer-cell receptor reexpression. · source_derived_draft · unverified_draft

    ## butyrate-hcar2-restoration Restoring the receptor enabled a response distinct from the HDAC pathway. Restoring GPR109A expression in human colon cancer cells enabled apoptosis in the presence of butyrate or nicotinate; the receptor-mediated response did not require histone deacetylation inhibition. Model: Human colon cancer-cell receptor reexpression. Limitations: An engineered culture rescue does not show that oral supplements restore silenced receptors in patients. Evidence access: Primary abstract GPR109A is a G-protein-coupled receptor for the bacterial fermentation product butyrate and functions as a tumor suppressor in colon. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19276343/ · DOI 10.1158/0008-5472.CAN-08-4466
    Complete structured claim and evidence

  2. Nicotinic-acid activation of GPR109A/HCAR2 in the human cell-line assay lowered cAMP through a pertussis-toxin-sensitive pathway.

    Human hydroxycarboxylic acid receptor 2 / HCAR2 → Intracellular cyclic AMP content source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    Nicotinic acid (agonist); Cyclic adenosine monophosphate (measured_signal)
    evidence_span
    {"source_cache": "artifacts/niacin-clinical-sources/walters2009.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "2eb822534ed0c8ea9f71ec67288c302e4e375ed9e86cfe70b28f21ae65ffbd4b", "start_char": 0, "end_char": 1537, "text_sha256": "2eb822534ed0c8ea9f71ec67288c302e4e375ed9e86cfe70b28f21ae65ffbd4b"}
    experimental_model
    Human cell-line nicotinic-acid receptor signaling assay
    exposure
    Nicotinic-acid stimulation and beta-arrestin perturbation
    limitations
    Pharmacological receptor signaling, not an essential effect of every B3 precursor. Cell signaling and mouse physiology are distinct arms. Reduced fatty acids or flushing does not establish cardiovascular benefit.
    nutrient_topic
    Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
    organism
    Homo sapiens
    plain_language
    Nicotinic acid can act as a receptor signal as well as a vitamin precursor, switching down a cellular signaling molecule.
    primary_references
    [nia-clin-walters2009] beta-Arrestin1 mediates nicotinic acid-induced flushing, but not its antilipolytic effect, in mice. (2009). https://pubmed.ncbi.nlm.nih.gov/19349687/ DOI: 10.1172/jci36806
    tissue_or_cell_type
    Cultured human cells

    Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 1291–1303

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human cell-line nicotinic-acid receptor signaling assay · source_derived_draft · unverified_draft

    ### nia-clin-hcar2-camp Nicotinic-acid activation of GPR109A/HCAR2 in the human cell-line assay lowered cAMP through a pertussis-toxin-sensitive pathway. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Nicotinic acid can act as a receptor signal as well as a vitamin precursor, switching down a cellular signaling molecule. organism: Homo sapiens tissue_or_cell_type: Cultured human cells experimental_model: Human cell-line nicotinic-acid receptor signaling assay limitations: Pharmacological receptor signaling, not an essential effect of every B3 precursor. Cell signaling and mouse physiology are distinct arms. Reduced fatty acids or flushing does not establish cardiovascular benefit. exposure: Nicotinic-acid stimulation and beta-arrestin perturbation cross_nutrient: Nicotinic acid (agonist); Cyclic adenosine monophosphate (measured_signal) evidence_span: {"source_cache": "artifacts/niacin-clinical-sources/walters2009.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "2eb822534ed0c8ea9f71ec67288c302e4e375ed9e86cfe70b28f21ae65ffbd4b", "start_char": 0, "end_char": 1537, "text_sha256": "2eb822534ed0c8ea9f71ec67288c302e4e375ed9e86cfe70b28f21ae65ffbd4b"} [nia-clin-walters2009] beta-Arrestin1 mediates nicotinic acid-induced flushing, but not its antilipolytic effect, in mice. (2009). https://pubmed.ncbi.nlm.nih.gov/19349687/ DOI: 10.1172/jci36806
    Complete structured claim and evidence

What acts on it

  1. Butyrate activated GPR109A/HCAR2 at millimolar concentrations in the study of receptor signaling in human colonic cells.

    Butyrate → Human hydroxycarboxylic acid receptor 2 / HCAR2 source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Human receptor/cell assays with separate mouse tissue observations.
    limitations
    Low affinity makes exposure compartment important; sharing a receptor does not make butyrate and niacin nutritionally interchangeable.
    nutrient_topic
    Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
    plain_language
    A receptor also used by nicotinic acid senses sufficiently high local butyrate.
    primary_references
    GPR109A is a G-protein-coupled receptor for the bacterial fermentation product butyrate and functions as a tumor suppressor in colon. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19276343/ · DOI 10.1158/0008-5472.CAN-08-4466

    Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 350–356

    AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human receptor/cell assays with separate mouse tissue observations. · source_derived_draft · unverified_draft

    ## butyrate-hcar2-agonism A receptor also used by nicotinic acid senses sufficiently high local butyrate. Butyrate activated GPR109A/HCAR2 at millimolar concentrations in the study of receptor signaling in human colonic cells. Model: Human receptor/cell assays with separate mouse tissue observations. Limitations: Low affinity makes exposure compartment important; sharing a receptor does not make butyrate and niacin nutritionally interchangeable. Evidence access: Primary abstract GPR109A is a G-protein-coupled receptor for the bacterial fermentation product butyrate and functions as a tumor suppressor in colon. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19276343/ · DOI 10.1158/0008-5472.CAN-08-4466
    Complete structured claim and evidence

  2. D-beta-hydroxybutyrate activated human HM74a/HCAR2 and its mouse orthologue.

    D-(R)-beta-hydroxybutyrate → Human hydroxycarboxylic acid receptor 2 / HCAR2 source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Human and mouse receptor pharmacology.
    limitations
    Shared receptor does not imply identical exposures or clinical effects.
    nutrient_topic
    Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake
    plain_language
    A fasting-associated ketone uses a receptor also used by nicotinic acid.
    primary_references
    (D)-beta-Hydroxybutyrate inhibits adipocyte lipolysis via the nicotinic acid receptor PUMA-G. · 2005 · https://pubmed.ncbi.nlm.nih.gov/15929991/ · DOI 10.1074/jbc.C500213200

    Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18) · lines 352–358

    AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human and mouse receptor pharmacology. · source_derived_draft · unverified_draft

    ## fast-bhb-hcar2 A fasting-associated ketone uses a receptor also used by nicotinic acid. D-beta-hydroxybutyrate activated human HM74a/HCAR2 and its mouse orthologue. Model: Human and mouse receptor pharmacology. Limitations: Shared receptor does not imply identical exposures or clinical effects. Evidence access: Primary abstract (D)-beta-Hydroxybutyrate inhibits adipocyte lipolysis via the nicotinic acid receptor PUMA-G. · 2005 · https://pubmed.ncbi.nlm.nih.gov/15929991/ · DOI 10.1074/jbc.C500213200
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. GPR109A/G-protein inhibition did not remove the tested human monocyte/macrophage anti-inflammatory response to butyrate; HDAC3-related mechanisms were implicated.

    Butyrate → Cytokine output of butyrate-treated human IBD biopsies source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Human monocytes and THP-1 macrophage experiments.
    limitations
    This does not negate the distinct mouse epithelial IL-18 dependency.
    nutrient_topic
    Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
    plain_language
    A receptor important in some models was not required for this tested response.
    primary_references
    Butyrate suppresses mucosal inflammation in inflammatory bowel disease primarily through HDAC3 inhibition in monocytes and macrophages. · 2025 · https://pubmed.ncbi.nlm.nih.gov/41110099/ · DOI 10.1111/febs.70289

    Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 430–436

    AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human monocytes and THP-1 macrophage experiments. · source_derived_draft · unverified_draft

    ## butyrate-ibd-hcar2-not-required A receptor important in some models was not required for this tested response. GPR109A/G-protein inhibition did not remove the tested human monocyte/macrophage anti-inflammatory response to butyrate; HDAC3-related mechanisms were implicated. Model: Human monocytes and THP-1 macrophage experiments. Limitations: This does not negate the distinct mouse epithelial IL-18 dependency. Evidence access: Primary abstract Butyrate suppresses mucosal inflammation in inflammatory bowel disease primarily through HDAC3 inhibition in monocytes and macrophages. · 2025 · https://pubmed.ncbi.nlm.nih.gov/41110099/ · DOI 10.1111/febs.70289
    Complete structured claim and evidence

  2. Nicotinic acid promoted beta-arrestin1 association with activated cytosolic phospholipase A2 and beta-arrestin1-dependent phospholipase activation with arachidonate release in the cell assay.

    Human beta-arrestin 1 / ARRB1 → Human cytosolic phospholipase A2 alpha / PLA2G4A source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    Human hydroxycarboxylic acid receptor 2 / HCAR2 (upstream_receptor); Nicotinic acid (agonist); arachidonic acid (released_substrate)
    evidence_span
    {"source_cache": "artifacts/niacin-clinical-sources/walters2009.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "2eb822534ed0c8ea9f71ec67288c302e4e375ed9e86cfe70b28f21ae65ffbd4b", "start_char": 0, "end_char": 1537, "text_sha256": "2eb822534ed0c8ea9f71ec67288c302e4e375ed9e86cfe70b28f21ae65ffbd4b"}
    experimental_model
    Human cell-line nicotinic-acid receptor signaling assay
    exposure
    Nicotinic-acid stimulation and beta-arrestin perturbation
    limitations
    Pharmacological receptor signaling, not an essential effect of every B3 precursor. Cell signaling and mouse physiology are distinct arms. Reduced fatty acids or flushing does not establish cardiovascular benefit.
    nutrient_topic
    Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
    organism
    Homo sapiens
    plain_language
    A separate receptor branch recruits beta-arrestin and releases the fatty-acid material used to make flushing signals.
    primary_references
    [nia-clin-walters2009] beta-Arrestin1 mediates nicotinic acid-induced flushing, but not its antilipolytic effect, in mice. (2009). https://pubmed.ncbi.nlm.nih.gov/19349687/ DOI: 10.1172/jci36806
    tissue_or_cell_type
    Cultured human cells

    Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 1305–1317

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human cell-line nicotinic-acid receptor signaling assay · source_derived_draft · unverified_draft

    ### nia-clin-arrb1-pla2 Nicotinic acid promoted beta-arrestin1 association with activated cytosolic phospholipase A2 and beta-arrestin1-dependent phospholipase activation with arachidonate release in the cell assay. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A separate receptor branch recruits beta-arrestin and releases the fatty-acid material used to make flushing signals. organism: Homo sapiens tissue_or_cell_type: Cultured human cells experimental_model: Human cell-line nicotinic-acid receptor signaling assay limitations: Pharmacological receptor signaling, not an essential effect of every B3 precursor. Cell signaling and mouse physiology are distinct arms. Reduced fatty acids or flushing does not establish cardiovascular benefit. exposure: Nicotinic-acid stimulation and beta-arrestin perturbation cross_nutrient: Human hydroxycarboxylic acid receptor 2 / HCAR2 (upstream_receptor); Nicotinic acid (agonist); arachidonic acid (released_substrate) evidence_span: {"source_cache": "artifacts/niacin-clinical-sources/walters2009.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "2eb822534ed0c8ea9f71ec67288c302e4e375ed9e86cfe70b28f21ae65ffbd4b", "start_char": 0, "end_char": 1537, "text_sha256": "2eb822534ed0c8ea9f71ec67288c302e4e375ed9e86cfe70b28f21ae65ffbd4b"} [nia-clin-walters2009] beta-Arrestin1 mediates nicotinic acid-induced flushing, but not its antilipolytic effect, in mice. (2009). https://pubmed.ncbi.nlm.nih.gov/19349687/ DOI: 10.1172/jci36806
    Complete structured claim and evidence

In the sources

Preserved passages that mention this component, quoted exactly. Open one to read it in context.

    This is a research prototype built from draft material. It is not medical advice, and its statements still await verification against the original studies.

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