Component

Mouse Hcar2 / PUMA-G receptor

Mouse Hcar2 / PUMA-G receptor. The model and exposure of each linked claim define its scope.

7 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. Butyrate-induced Il18 expression in mouse colonic epithelium required Gpr109a/Hcar2.

    Mouse Hcar2 / PUMA-G receptor → Mouse interleukin-18 / Il18 source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary abstract
    experimental_model
    Mouse Hcar2 knockout and epithelial stimulation.
    limitations
    IL-18 has context-dependent functions; this does not mean all inflammasome activation is beneficial.
    nutrient_topic
    Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
    plain_language
    Receptor loss removed a specific epithelial cytokine response.
    primary_references
    Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis. · 2014 · https://pubmed.ncbi.nlm.nih.gov/24412617/ · DOI 10.1016/j.immuni.2013.12.007
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 382–388

    AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Mouse Hcar2 knockout and epithelial stimulation. · source_derived_draft · unverified_draft

    ## butyrate-hcar2-il18 Receptor loss removed a specific epithelial cytokine response. Butyrate-induced Il18 expression in mouse colonic epithelium required Gpr109a/Hcar2. Model: Mouse Hcar2 knockout and epithelial stimulation. Limitations: IL-18 has context-dependent functions; this does not mean all inflammasome activation is beneficial. Evidence access: Primary abstract Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis. · 2014 · https://pubmed.ncbi.nlm.nih.gov/24412617/ · DOI 10.1016/j.immuni.2013.12.007
    Complete structured claim and evidence

  2. Hcar2-deficient mice lost the reported protective response to butyrate in Adriamycin nephropathy.

    Mouse Hcar2 / PUMA-G receptor → Mouse podocyte injury and proteinuria after butyrate source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary abstract
    experimental_model
    Mouse receptor knockout during induced nephropathy.
    limitations
    Does not establish the same dependency for human IBD monocytes or all kidney injury.
    nutrient_topic
    Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
    plain_language
    The kidney response required a receptor in this model.
    primary_references
    Gut microbial metabolite butyrate protects against proteinuric kidney disease through epigenetic- and GPR109a-mediated mechanisms. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31366236/ · DOI 10.1096/fj.201901080R
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 614–620

    AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Mouse receptor knockout during induced nephropathy. · source_derived_draft · unverified_draft

    ## butyrate-kidney-hcar2-loss The kidney response required a receptor in this model. Hcar2-deficient mice lost the reported protective response to butyrate in Adriamycin nephropathy. Model: Mouse receptor knockout during induced nephropathy. Limitations: Does not establish the same dependency for human IBD monocytes or all kidney injury. Evidence access: Primary abstract Gut microbial metabolite butyrate protects against proteinuric kidney disease through epigenetic- and GPR109a-mediated mechanisms. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31366236/ · DOI 10.1096/fj.201901080R
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. Butyrate promoted Aldh1a1 and Il10 expression in mouse dendritic/macrophage experiments through Gpr109a signaling.

    Butyrate → Mouse aldehyde dehydrogenase 1 family member A1 / Aldh1a1 source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary full text, Figure 2
    experimental_model
    Mouse immune-cell stimulation and Hcar2-deficient comparisons.
    limitations
    ALDH expression does not by itself measure retinoic-acid flux or establish dietary vitamin A deficiency.
    nutrient_topic
    Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
    plain_language
    A butyrate signal connected to vitamin A processing and immune regulation.
    primary_references
    Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis. · 2014 · https://pubmed.ncbi.nlm.nih.gov/24412617/ · DOI 10.1016/j.immuni.2013.12.007

    Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 366–372

    AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Mouse immune-cell stimulation and Hcar2-deficient comparisons. · source_derived_draft · unverified_draft

    ## butyrate-aldh1a1-immune A butyrate signal connected to vitamin A processing and immune regulation. Butyrate promoted Aldh1a1 and Il10 expression in mouse dendritic/macrophage experiments through Gpr109a signaling. Model: Mouse immune-cell stimulation and Hcar2-deficient comparisons. Limitations: ALDH expression does not by itself measure retinoic-acid flux or establish dietary vitamin A deficiency. Evidence access: Primary full text, Figure 2 Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis. · 2014 · https://pubmed.ncbi.nlm.nih.gov/24412617/ · DOI 10.1016/j.immuni.2013.12.007
    Complete structured claim and evidence

  2. Sodium butyrate reduced proteinuria, podocyte loss and renal injury in the mouse Adriamycin-nephropathy study.

    Butyrate → Mouse podocyte injury and proteinuria after butyrate source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Mouse induced-nephropathy intervention, with a separate butyrate-releasing starch arm.
    limitations
    Not evidence of efficacy in all human kidney diseases.
    nutrient_topic
    Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate
    plain_language
    The experimental benefit extended beyond the gut to the kidney.
    primary_references
    Gut microbial metabolite butyrate protects against proteinuric kidney disease through epigenetic- and GPR109a-mediated mechanisms. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31366236/ · DOI 10.1096/fj.201901080R

    Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 606–612

    AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Mouse induced-nephropathy intervention, with a separate butyrate-releasing starch arm. · source_derived_draft · unverified_draft

    ## butyrate-kidney-protection The experimental benefit extended beyond the gut to the kidney. Sodium butyrate reduced proteinuria, podocyte loss and renal injury in the mouse Adriamycin-nephropathy study. Model: Mouse induced-nephropathy intervention, with a separate butyrate-releasing starch arm. Limitations: Not evidence of efficacy in all human kidney diseases. Evidence access: Primary abstract Gut microbial metabolite butyrate protects against proteinuric kidney disease through epigenetic- and GPR109a-mediated mechanisms. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31366236/ · DOI 10.1096/fj.201901080R
    Complete structured claim and evidence

  3. PUMA-G-deficient mice did not flush after nicotinic acid; transplantation of wild-type bone marrow restored this response.

    Mouse Hcar2 knockout genotype → Nicotinic-acid-induced cutaneous flushing source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    cross_nutrient
    Nicotinic acid (agonist); Mouse Hcar2 / PUMA-G receptor (affected_receptor)
    evidence_span
    {"source_cache": "artifacts/niacin-clinical-sources/benyo2005.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "21dedb52cbd8fccaf810dabec7837e471525e0a5462827b21437d2f7b30c44a2", "start_char": 0, "end_char": 1388, "text_sha256": "21dedb52cbd8fccaf810dabec7837e471525e0a5462827b21437d2f7b30c44a2"}
    experimental_model
    PUMA-G/Hcar2 and prostaglandin-pathway mouse knockout experiments with bone-marrow transplantation
    exposure
    Nicotinic acid; receptor or cyclooxygenase deletion; wild-type bone-marrow rescue
    limitations
    Mouse pharmacological flushing experiment. HCAR2 historically GPR109A/HM74A in humans; mouse receptor PUMA-G. The location of the responsible immune cells was inferred, not every human flush directly measured.
    nutrient_topic
    Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
    organism
    Mus musculus
    plain_language
    The mouse flushing signal required the receptor in a population supplied by bone marrow.
    primary_references
    [nia-clin-benyo2005] GPR109A (PUMA-G/HM74A) mediates nicotinic acid-induced flushing. (2005). https://pubmed.ncbi.nlm.nih.gov/16322797/ DOI: 10.1172/jci23626
    tissue_or_cell_type
    Skin vasculature and hematopoietic cells
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 1333–1345

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · PUMA-G/Hcar2 and prostaglandin-pathway mouse knockout experiments with bone-marrow transplantation · source_derived_draft · unverified_draft

    ### nia-clin-hcar2-mouse-flush PUMA-G-deficient mice did not flush after nicotinic acid; transplantation of wild-type bone marrow restored this response. Condition category: machinery_impairment nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The mouse flushing signal required the receptor in a population supplied by bone marrow. organism: Mus musculus tissue_or_cell_type: Skin vasculature and hematopoietic cells experimental_model: PUMA-G/Hcar2 and prostaglandin-pathway mouse knockout experiments with bone-marrow transplantation limitations: Mouse pharmacological flushing experiment. HCAR2 historically GPR109A/HM74A in humans; mouse receptor PUMA-G. The location of the responsible immune cells was inferred, not every human flush directly measured. exposure: Nicotinic acid; receptor or cyclooxygenase deletion; wild-type bone-marrow rescue cross_nutrient: Nicotinic acid (agonist); Mouse Hcar2 / PUMA-G receptor (affected_receptor) evidence_span: {"source_cache": "artifacts/niacin-clinical-sources/benyo2005.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "21dedb52cbd8fccaf810dabec7837e471525e0a5462827b21437d2f7b30c44a2", "start_char": 0, "end_char": 1388, "text_sha256": "21dedb52cbd8fccaf810dabec7837e471525e0a5462827b21437d2f7b30c44a2"} [nia-clin-benyo2005] GPR109A (PUMA-G/HM74A) mediates nicotinic acid-induced flushing. (2005). https://pubmed.ncbi.nlm.nih.gov/16322797/ DOI: 10.1172/jci23626
    Complete structured claim and evidence

  4. 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

  5. D-beta-hydroxybutyrate inhibited mouse adipocyte lipolysis in an Hcar2-dependent manner.

    D-(R)-beta-hydroxybutyrate → Mouse adipocyte lipolysis source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Mouse adipocyte experiments.
    limitations
    Whole-body ketone feedback was proposed; magnitude in human fasting was not established.
    nutrient_topic
    Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake
    plain_language
    A ketone could feed back on its upstream fuel supply.
    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 360–366

    AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Mouse adipocyte experiments. · source_derived_draft · unverified_draft

    ## fast-bhb-lipolysis-feedback A ketone could feed back on its upstream fuel supply. D-beta-hydroxybutyrate inhibited mouse adipocyte lipolysis in an Hcar2-dependent manner. Model: Mouse adipocyte experiments. Limitations: Whole-body ketone feedback was proposed; magnitude in human fasting was not established. 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

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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