Human PPAR gamma / PPARG

evidence_access

Primary abstract

experimental_model

Human corneal epithelial cell culture.

limitations

Not an oral dry-eye treatment trial.

nutrient_topic

Luteolin collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Luteolin / 3′,4′,5,7-tetrahydroxyflavone

plain_language

An eye-surface model links inflammation and barrier function.

primary_references

Mode of peroxisome proliferator-activated receptor γ activation by luteolin. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22391103/ · DOI 10.1124/mol.111.076216

Luteolin: metabolism, immune signaling, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 380–386

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human corneal epithelial cell culture. · source_derived_draft · unverified_draft

## luteolin-pparg-corneal An eye-surface model links inflammation and barrier function. Luteolin reduced IL-8 release and restored electrical resistance in hypertonic human corneal epithelial cultures through a PPAR gamma-dependent response. Model: Human corneal epithelial cell culture. Limitations: Not an oral dry-eye treatment trial. Evidence access: Primary abstract Mode of peroxisome proliferator-activated receptor γ activation by luteolin. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22391103/ · DOI 10.1124/mol.111.076216

evidence_span

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experimental_model

Neuron-like PC12 and B104 cells and primary cultured neurons with small interfering RNA knockdown

exposure

Ibuprofen with peroxisome proliferator-activated receptor gamma agonists, antagonists and knockdown

limitations

The knockdown and the selective antagonist together make the receptor requirement a test rather than a correlation. Cell lines and primary culture rather than an animal.

nutrient_topic

Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. · Ibuprofen

organism

Rat

plain_language

The drug reaches a growth-blocking switch in neurons through a fat-sensing receptor, not through prostaglandins.

primary_references

[ibu-p20089905] A molecular mechanism for ibuprofen-mediated RhoA inhibition in neurons. (2010). https://pubmed.ncbi.nlm.nih.gov/20089905/ DOI: 10.1523/jneurosci.5045-09.2010

tissue_or_cell_type

Neurons

Ibuprofen: the enantiomer that works, the one that was called inactive, the one-way chemistry that turns one into the other, and the targets that are not cyclooxygenase (2026-09-22) · lines 422–433

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Neuron-like PC12 and B104 cells and primary cultured neurons with small interfering RNA knockdown · source_derived_draft · unverified_draft

### ibu-pparg-couples-to-rhoa Ibuprofen activates peroxisome proliferator-activated receptor gamma in neuron-like PC12 and B104 cells, activation with traditional agonists mimics the RhoA-inhibiting properties of ibuprofen and promotes neurite elongation in primary neurons exposed to axonal growth inhibitors, small interfering RNA against the receptor blocks RhoA suppression by those agonists, and selective receptor inhibition prevents the effect of ibuprofen on RhoA activity and neurite growth, supporting an essential role for the receptor in coupling ibuprofen to RhoA inhibition. Condition category: normal nutrient_topic: Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. plain_language: The drug reaches a growth-blocking switch in neurons through a fat-sensing receptor, not through prostaglandins. organism: Rat tissue_or_cell_type: Neurons experimental_model: Neuron-like PC12 and B104 cells and primary cultured neurons with small interfering RNA knockdown limitations: The knockdown and the selective antagonist together make the receptor requirement a test rather than a correlation. Cell lines and primary culture rather than an animal. exposure: Ibuprofen with peroxisome proliferator-activated receptor gamma agonists, antagonists and knockdown evidence_span: {"source_cache": "artifacts/ibuprofen-research/20089905.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "77e2dbb010dcee44bd66645ec26cb844d7041ea4930f6373ae5dd6b10da37df3", "start_char": 0, "end_char": 1812, "text_sha256": "77e2dbb010dcee44bd66645ec26cb844d7041ea4930f6373ae5dd6b10da37df3"} [ibu-p20089905] A molecular mechanism for ibuprofen-mediated RhoA inhibition in neurons. (2010). https://pubmed.ncbi.nlm.nih.gov/20089905/ DOI: 10.1523/jneurosci.5045-09.2010

evidence_access

Primary abstract

experimental_model

PPAR gamma ligand-binding-domain crystallography.

limitations

Simulated cooperative stabilization is not demonstrated nutritional synergy.

nutrient_topic

Luteolin collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Luteolin / 3′,4′,5,7-tetrahydroxyflavone

plain_language

Two ligands fit in the structural preparation.

primary_references

Mode of peroxisome proliferator-activated receptor γ activation by luteolin. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22391103/ · DOI 10.1124/mol.111.076216

Luteolin: metabolism, immune signaling, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 364–370

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · PPAR gamma ligand-binding-domain crystallography. · source_derived_draft · unverified_draft

## luteolin-pparg-ligand Two ligands fit in the structural preparation. Luteolin occupied the PPAR gamma ligand pocket in an inactive conformer; myristic acid simultaneously occupied the pocket. Model: PPAR gamma ligand-binding-domain crystallography. Limitations: Simulated cooperative stabilization is not demonstrated nutritional synergy. Evidence access: Primary abstract Mode of peroxisome proliferator-activated receptor γ activation by luteolin. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22391103/ · DOI 10.1124/mol.111.076216

evidence_span

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experimental_model

IL-1beta-stimulated osteoarthritis chondrocytes with inhibitor perturbation

exposure

Mangiferin with IL-1beta; PPAR-gamma inhibitor GW9662

limitations

Cell experiment, not a clinical arthritis trial; inhibitor reversal supports involvement but not direct receptor agonism.

nutrient_topic

Mangiferin research collection; topical membership is not evidence of a direct dietary effect. · Mangiferin

organism

Homo sapiens

plain_language

A transcriptional regulator participated in the response.

primary_references

[mangiferin-p27734234] Mangiferin Inhibits IL-1β-Induced Inflammatory Response by Activating PPAR-γ in Human Osteoarthritis Chondrocytes. (2017). https://pubmed.ncbi.nlm.nih.gov/27734234/ DOI: 10.1007/s10753-016-0451-y

tissue_or_cell_type

Cultured chondrocytes

Mangiferin: metabolism, signaling and nutrient connections (2026-09-17) · lines 1316–1327

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · IL-1beta-stimulated osteoarthritis chondrocytes with inhibitor perturbation · source_derived_draft · unverified_draft

### mangiferin-pparg Mangiferin increased PPAR-gamma expression in the chondrocyte experiment. Condition category: normal nutrient_topic: Mangiferin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A transcriptional regulator participated in the response. organism: Homo sapiens tissue_or_cell_type: Cultured chondrocytes experimental_model: IL-1beta-stimulated osteoarthritis chondrocytes with inhibitor perturbation limitations: Cell experiment, not a clinical arthritis trial; inhibitor reversal supports involvement but not direct receptor agonism. exposure: Mangiferin with IL-1beta; PPAR-gamma inhibitor GW9662 evidence_span: {"source_cache": "artifacts/mangiferin-research/27734234.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1b9924d15171028fb1006c5e72c7b0dc6742d96f6873a292e6f5741061ad2f44", "start_char": 0, "end_char": 1007, "text_sha256": "1b9924d15171028fb1006c5e72c7b0dc6742d96f6873a292e6f5741061ad2f44"} [mangiferin-p27734234] Mangiferin Inhibits IL-1β-Induced Inflammatory Response by Activating PPAR-γ in Human Osteoarthritis Chondrocytes. (2017). https://pubmed.ncbi.nlm.nih.gov/27734234/ DOI: 10.1007/s10753-016-0451-y

evidence_access

Primary full text, methods 2.4 and SPR results

experimental_model

Recombinant human receptor-domain biochemistry.

limitations

Reporter effects depend on construct, cell and coactivator context.

nutrient_topic

Astaxanthin collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Astaxanthin

plain_language

Direct binding and the direction of transcriptional effects are separate questions.

primary_references

The natural carotenoid astaxanthin, a PPAR-α agonist and PPAR-γ antagonist, reduces hepatic lipid accumulation by rewiring the transcriptome in lipid-loaded hepatocytes. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22707263/ · DOI 10.1002/mnfr.201100798

Astaxanthin: transport, membrane chemistry, signaling and nutrient interactions (2026-09-19) · lines 254–260

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Recombinant human receptor-domain biochemistry. · source_derived_draft · unverified_draft

## astaxanthin-pparg-binding Direct binding and the direction of transcriptional effects are separate questions. Surface-plasmon-resonance assays detected binding of astaxanthin to recombinant human PPAR-gamma ligand-binding domains. Model: Recombinant human receptor-domain biochemistry. Limitations: Reporter effects depend on construct, cell and coactivator context. Evidence access: Primary full text, methods 2.4 and SPR results The natural carotenoid astaxanthin, a PPAR-α agonist and PPAR-γ antagonist, reduces hepatic lipid accumulation by rewiring the transcriptome in lipid-loaded hepatocytes. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22707263/ · DOI 10.1002/mnfr.201100798

evidence_access

Primary abstract

experimental_model

Primary cultures of differentiating human preadipocytes.

limitations

Not proof of improved insulin sensitivity in humans.

nutrient_topic

CLA collection; isomer, preparation, species, exposure and manipulation remain explicit. · Conjugated linoleic acid / CLA isomer family

plain_language

The other isomer gave a different transcriptional response.

primary_references

Isomer-specific regulation of metabolism and PPARgamma signaling by CLA in human preadipocytes. · 2003 · https://pubmed.ncbi.nlm.nih.gov/12730300/ · DOI 10.1194/jlr.M300001-JLR200

Conjugated linoleic acid: isomers, signaling, nutrient interactions and discovery (2026-09-19) · lines 94–100

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Primary cultures of differentiating human preadipocytes. · source_derived_draft · unverified_draft

## cla-pparg-expression-c9 The other isomer gave a different transcriptional response. Adding c9,t11 CLA increased PPAR-gamma and several target-gene transcripts relative to vehicle. Model: Primary cultures of differentiating human preadipocytes. Limitations: Not proof of improved insulin sensitivity in humans. Evidence access: Primary abstract Isomer-specific regulation of metabolism and PPARgamma signaling by CLA in human preadipocytes. · 2003 · https://pubmed.ncbi.nlm.nih.gov/12730300/ · DOI 10.1194/jlr.M300001-JLR200

evidence_access

Primary abstract

experimental_model

Primary cultures of differentiating human preadipocytes.

limitations

Expression and direct ligand binding are different measurements.

nutrient_topic

CLA collection; isomer, preparation, species, exposure and manipulation remain explicit. · Conjugated linoleic acid / CLA isomer family

plain_language

A regulator of fat-cell identity was suppressed.

primary_references

Isomer-specific regulation of metabolism and PPARgamma signaling by CLA in human preadipocytes. · 2003 · https://pubmed.ncbi.nlm.nih.gov/12730300/ · DOI 10.1194/jlr.M300001-JLR200

Conjugated linoleic acid: isomers, signaling, nutrient interactions and discovery (2026-09-19) · lines 86–92

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Primary cultures of differentiating human preadipocytes. · source_derived_draft · unverified_draft

## cla-pparg-expression-t10 A regulator of fat-cell identity was suppressed. Adding t10,c12 CLA lowered PPAR-gamma and several target-gene transcripts. Model: Primary cultures of differentiating human preadipocytes. Limitations: Expression and direct ligand binding are different measurements. Evidence access: Primary abstract Isomer-specific regulation of metabolism and PPARgamma signaling by CLA in human preadipocytes. · 2003 · https://pubmed.ncbi.nlm.nih.gov/12730300/ · DOI 10.1194/jlr.M300001-JLR200

evidence_access

Primary abstract

experimental_model

Human adipocyte time-course experiments.

limitations

ERK causation of the PPAR-gamma phosphorylation was proposed rather than isolated here.

nutrient_topic

CLA collection; isomer, preparation, species, exposure and manipulation remain explicit. · Conjugated linoleic acid / CLA isomer family

plain_language

Signaling changed before the regulator became less abundant.

primary_references

Trans-10, cis-12 conjugated linoleic acid antagonizes ligand-dependent PPARgamma activity in primary cultures of human adipocytes. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18287349/ · DOI 10.1093/jn/138.3.455

Conjugated linoleic acid: isomers, signaling, nutrient interactions and discovery (2026-09-19) · lines 110–116

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

## cla-pparg-phosphorylation Signaling changed before the regulator became less abundant. Adding t10,c12 CLA increased PPAR-gamma and ERK1/2 phosphorylation before PPAR-gamma protein declined. Model: Human adipocyte time-course experiments. Limitations: ERK causation of the PPAR-gamma phosphorylation was proposed rather than isolated here. Evidence access: Primary abstract Trans-10, cis-12 conjugated linoleic acid antagonizes ligand-dependent PPARgamma activity in primary cultures of human adipocytes. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18287349/ · DOI 10.1093/jn/138.3.455

evidence_span

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experimental_model

Reporter and enzyme assays comparing ibuprofen isomers against naproxen and indomethacin across four readouts

exposure

S(+)- and R(-)-ibuprofen compared directly on cyclooxygenase-1 and -2, platelet function and nuclear receptor activation

limitations

The only record here that measures both enantiomers on the same panel, which is what makes the fold-differences meaningful. Several different assay systems are combined.

nutrient_topic

Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. · Ibuprofen

organism

Rat, human and sheep systems

plain_language

Both hands switch on the fat-handling nuclear receptors, with a much smaller gap between them than at cyclooxygenase.

primary_references

[ibu-p11755111] Activation of peroxisome proliferator-activated receptor isoforms and inhibition of prostaglandin H(2) synthases by ibuprofen, naproxen, and indomethacin. (2001). https://pubmed.ncbi.nlm.nih.gov/11755111/ DOI: 10.1016/s0006-2952(01)00822-x

tissue_or_cell_type

Transfected cells, hepatoma cells, platelets and purified enzyme

Ibuprofen: the enantiomer that works, the one that was called inactive, the one-way chemistry that turns one into the other, and the targets that are not cyclooxygenase (2026-09-22) · lines 331–342

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Reporter and enzyme assays comparing ibuprofen isomers against naproxen and indomethacin across four readouts · source_derived_draft · unverified_draft

### ibu-both-isomers-hit-ppar Each drug tested produced concentration-dependent activation of peroxisome proliferator-activated receptor alpha and gamma isoforms and of peroxisomal fatty acyl-CoA beta-oxidase activity, with a rank order of stereoselectivity for alpha activation and fatty acyl oxidase stimulation of S(+)-ibuprofen greater than R(-)-ibuprofen, S(+)-ibuprofen being more potent than indomethacin and naproxen on these parameters, while on gamma the order was S(+)-naproxen greater than indomethacin greater than S(+)-ibuprofen greater than R(-)-ibuprofen. Condition category: normal nutrient_topic: Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. plain_language: Both hands switch on the fat-handling nuclear receptors, with a much smaller gap between them than at cyclooxygenase. organism: Rat, human and sheep systems tissue_or_cell_type: Transfected cells, hepatoma cells, platelets and purified enzyme experimental_model: Reporter and enzyme assays comparing ibuprofen isomers against naproxen and indomethacin across four readouts limitations: The only record here that measures both enantiomers on the same panel, which is what makes the fold-differences meaningful. Several different assay systems are combined. exposure: S(+)- and R(-)-ibuprofen compared directly on cyclooxygenase-1 and -2, platelet function and nuclear receptor activation evidence_span: {"source_cache": "artifacts/ibuprofen-research/11755111.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1dd77f4a1eebd7777285c424b1731f4744d0fa593e62cfbde0a92dbb6242b239", "start_char": 0, "end_char": 2074, "text_sha256": "1dd77f4a1eebd7777285c424b1731f4744d0fa593e62cfbde0a92dbb6242b239"} [ibu-p11755111] Activation of peroxisome proliferator-activated receptor isoforms and inhibition of prostaglandin H(2) synthases by ibuprofen, naproxen, and indomethacin. (2001). https://pubmed.ncbi.nlm.nih.gov/11755111/ DOI: 10.1016/s0006-2952(01)00822-x

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

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experimental_model

IL-1beta-stimulated osteoarthritis chondrocytes with inhibitor perturbation

exposure

Mangiferin with IL-1beta; PPAR-gamma inhibitor GW9662

limitations

The indexed abstract reports reversal of anti-inflammatory effects collectively; endpoint-specific magnitude is unresolved.

nutrient_topic

Mangiferin research collection; topical membership is not evidence of a direct dietary effect. · Mangiferin

organism

Homo sapiens

plain_language

Blocking related machinery weakened the response.

primary_references

[mangiferin-p27734234] Mangiferin Inhibits IL-1β-Induced Inflammatory Response by Activating PPAR-γ in Human Osteoarthritis Chondrocytes. (2017). https://pubmed.ncbi.nlm.nih.gov/27734234/ DOI: 10.1007/s10753-016-0451-y

tissue_or_cell_type

Cultured chondrocytes

trigger_kind

machinery_impairment Imported condition classification; unverified.

Mangiferin: metabolism, signaling and nutrient connections (2026-09-17) · lines 1342–1353

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · IL-1beta-stimulated osteoarthritis chondrocytes with inhibitor perturbation · source_derived_draft · unverified_draft

### mangiferin-pparg-loss GW9662 reversed the anti-inflammatory effect of mangiferin in the chondrocyte study. Condition category: machinery_impairment nutrient_topic: Mangiferin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Blocking related machinery weakened the response. organism: Homo sapiens tissue_or_cell_type: Cultured chondrocytes experimental_model: IL-1beta-stimulated osteoarthritis chondrocytes with inhibitor perturbation limitations: The indexed abstract reports reversal of anti-inflammatory effects collectively; endpoint-specific magnitude is unresolved. exposure: Mangiferin with IL-1beta; PPAR-gamma inhibitor GW9662 evidence_span: {"source_cache": "artifacts/mangiferin-research/27734234.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1b9924d15171028fb1006c5e72c7b0dc6742d96f6873a292e6f5741061ad2f44", "start_char": 0, "end_char": 1007, "text_sha256": "1b9924d15171028fb1006c5e72c7b0dc6742d96f6873a292e6f5741061ad2f44"} [mangiferin-p27734234] Mangiferin Inhibits IL-1β-Induced Inflammatory Response by Activating PPAR-γ in Human Osteoarthritis Chondrocytes. (2017). https://pubmed.ncbi.nlm.nih.gov/27734234/ DOI: 10.1007/s10753-016-0451-y

evidence_access

Primary abstract

experimental_model

Human AGS expression assays and pharmacological inhibition.

limitations

Antagonist sensitivity is not direct binding evidence or a demonstration of iron deficiency rescue.

nutrient_topic

Astaxanthin collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Astaxanthin

plain_language

A receptor-linked antioxidant enzyme response contributed in this model.

primary_references

Astaxanthin Inhibits Mitochondrial Dysfunction and Interleukin-8 Expression in Helicobacter pylori-Infected Gastric Epithelial Cells. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30231525/ · DOI 10.3390/nu10091320

Astaxanthin: transport, membrane chemistry, signaling and nutrient interactions (2026-09-19) · lines 302–308

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human AGS expression assays and pharmacological inhibition. · source_derived_draft · unverified_draft

## astaxanthin-gastric-catalase A receptor-linked antioxidant enzyme response contributed in this model. Astaxanthin increased PPAR-gamma and catalase expression in challenged AGS cells; the PPAR-gamma antagonist GW9662 suppressed the ROS/IL-8 protective response. Model: Human AGS expression assays and pharmacological inhibition. Limitations: Antagonist sensitivity is not direct binding evidence or a demonstration of iron deficiency rescue. Evidence access: Primary abstract Astaxanthin Inhibits Mitochondrial Dysfunction and Interleukin-8 Expression in Helicobacter pylori-Infected Gastric Epithelial Cells. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30231525/ · DOI 10.3390/nu10091320

evidence_span

{"source_cache": "artifacts/cold-research/9529258.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8986da918d7bde4d0314f51038ee3b1c6413042a1132bb6fbf55ceeb54e79ddf", "start_char": 0, "end_char": 842, "text_sha256": "8986da918d7bde4d0314f51038ee3b1c6413042a1132bb6fbf55ceeb54e79ddf"}

experimental_model

Cloning of PGC-1 from a brown fat cDNA library with ectopic expression in white adipose cells

exposure

Cold exposure of mice; ectopic PGC-1 expression

limitations

The founding description of the coactivator. Ectopic expression shows sufficiency in white fat cells; it does not establish the size of the contribution in vivo.

nutrient_topic

Cold water immersion research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Cold water immersion

organism

Mouse

plain_language

Cold turns on a coactivator that switches the heat gene on through two different receptors.

primary_references

[cold-p9529258] A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis. (1998). https://pubmed.ncbi.nlm.nih.gov/9529258/ DOI: 10.1016/s0092-8674(00)81410-5

tissue_or_cell_type

Brown fat and skeletal muscle

Cold water immersion: cold sensing, heat production, the catecholamine axis and what repeated exposure changes (2026-09-19) · lines 338–349

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cloning of PGC-1 from a brown fat cDNA library with ectopic expression in white adipose cells · source_derived_draft · unverified_draft

### cold-pgc1a-cold-induction PGC-1 mRNA expression is dramatically elevated on cold exposure in both brown fat and skeletal muscle, and PGC-1 greatly increases the transcriptional activity of PPARgamma and the thyroid hormone receptor on the UCP1 promoter. Condition category: normal nutrient_topic: Cold water immersion research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: Cold turns on a coactivator that switches the heat gene on through two different receptors. organism: Mouse tissue_or_cell_type: Brown fat and skeletal muscle experimental_model: Cloning of PGC-1 from a brown fat cDNA library with ectopic expression in white adipose cells limitations: The founding description of the coactivator. Ectopic expression shows sufficiency in white fat cells; it does not establish the size of the contribution in vivo. exposure: Cold exposure of mice; ectopic PGC-1 expression evidence_span: {"source_cache": "artifacts/cold-research/9529258.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8986da918d7bde4d0314f51038ee3b1c6413042a1132bb6fbf55ceeb54e79ddf", "start_char": 0, "end_char": 842, "text_sha256": "8986da918d7bde4d0314f51038ee3b1c6413042a1132bb6fbf55ceeb54e79ddf"} [cold-p9529258] A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis. (1998). https://pubmed.ncbi.nlm.nih.gov/9529258/ DOI: 10.1016/s0092-8674(00)81410-5

evidence_access

Primary abstract

experimental_model

One-week co-treatment of primary human adipocyte cultures.

limitations

Transcript rescue did not restore all downstream functions.

nutrient_topic

CLA collection; isomer, preparation, species, exposure and manipulation remain explicit. · Conjugated linoleic acid / CLA isomer family

plain_language

Restoring some target genes did not restore the whole response.

primary_references

Trans-10, cis-12 conjugated linoleic acid antagonizes ligand-dependent PPARgamma activity in primary cultures of human adipocytes. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18287349/ · DOI 10.1093/jn/138.3.455

Conjugated linoleic acid: isomers, signaling, nutrient interactions and discovery (2026-09-19) · lines 118–124

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · One-week co-treatment of primary human adipocyte cultures. · source_derived_draft · unverified_draft

## cla-partial-rescue Restoring some target genes did not restore the whole response. BRL co-treatment rescued FABP4, LPL and perilipin transcripts but did not prevent reduced GLUT4, glucose uptake or triglyceride content. Model: One-week co-treatment of primary human adipocyte cultures. Limitations: Transcript rescue did not restore all downstream functions. Evidence access: Primary abstract Trans-10, cis-12 conjugated linoleic acid antagonizes ligand-dependent PPARgamma activity in primary cultures of human adipocytes. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18287349/ · DOI 10.1093/jn/138.3.455

evidence_access

Primary abstract

experimental_model

Primary human adipocyte culture and reporter experiments.

limitations

The 2003 transient-transfection study reported antagonism with both isomers; assay context remains relevant.

nutrient_topic

CLA collection; isomer, preparation, species, exposure and manipulation remain explicit. · Conjugated linoleic acid / CLA isomer family

plain_language

An isomer could interfere with activation of the regulator.

primary_references

Trans-10, cis-12 conjugated linoleic acid antagonizes ligand-dependent PPARgamma activity in primary cultures of human adipocytes. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18287349/ · DOI 10.1093/jn/138.3.455

Conjugated linoleic acid: isomers, signaling, nutrient interactions and discovery (2026-09-19) · lines 102–108

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

## cla-pparg-antagonism An isomer could interfere with activation of the regulator. Adding t10,c12, but not c9,t11 CLA, suppressed ligand-stimulated PPAR-gamma reporter activation. Model: Primary human adipocyte culture and reporter experiments. Limitations: The 2003 transient-transfection study reported antagonism with both isomers; assay context remains relevant. Evidence access: Primary abstract Trans-10, cis-12 conjugated linoleic acid antagonizes ligand-dependent PPARgamma activity in primary cultures of human adipocytes. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18287349/ · DOI 10.1093/jn/138.3.455

evidence_access

Primary abstract

experimental_model

Human adipocyte RNA-interference experiment.

limitations

Supports a contribution in this model, not universal necessity in all tissues.

nutrient_topic

CLA collection; isomer, preparation, species, exposure and manipulation remain explicit. · Conjugated linoleic acid / CLA isomer family

plain_language

Removing a signaling component weakened the adverse response.

primary_references

Conjugated linoleic acid promotes human adipocyte insulin resistance through NFkappaB-dependent cytokine production. · 2005 · https://pubmed.ncbi.nlm.nih.gov/16155293/ · DOI 10.1074/jbc.M508159200

Conjugated linoleic acid: isomers, signaling, nutrient interactions and discovery (2026-09-19) · lines 142–148

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

## cla-rela-knockdown Removing a signaling component weakened the adverse response. p65 siRNA depletion attenuated CLA-induced loss of GLUT4 and PPAR-gamma proteins and suppression of glucose uptake. Model: Human adipocyte RNA-interference experiment. Limitations: Supports a contribution in this model, not universal necessity in all tissues. Evidence access: Primary abstract Conjugated linoleic acid promotes human adipocyte insulin resistance through NFkappaB-dependent cytokine production. · 2005 · https://pubmed.ncbi.nlm.nih.gov/16155293/ · DOI 10.1074/jbc.M508159200

evidence_access

Primary abstract

experimental_model

Human colorectal cell line, 0–2.5 micromolar CLA.

limitations

Pharmacological support does not identify the active isomer or prove human mucosal healing.

nutrient_topic

CLA collection; isomer, preparation, species, exposure and manipulation remain explicit. · Conjugated linoleic acid / CLA isomer family

plain_language

A mucosal-repair protein responded through a receptor-sensitive pathway.

primary_references

Dietary conjugated linoleic acid activates PPARγ and the intestinal trefoil factor in SW480 cells and mice with dextran sulfate sodium-induced colitis. · 2012 · https://pubmed.ncbi.nlm.nih.gov/23077197/ · DOI 10.3945/jn.112.163931

Conjugated linoleic acid: isomers, signaling, nutrient interactions and discovery (2026-09-19) · lines 374–380

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human colorectal cell line, 0–2.5 micromolar CLA. · source_derived_draft · unverified_draft

## cla-tff3 A mucosal-repair protein responded through a receptor-sensitive pathway. CLA increased TFF3 in human SW480 cells; PPAR-gamma antagonist GW9662 prevented this induction. Model: Human colorectal cell line, 0–2.5 micromolar CLA. Limitations: Pharmacological support does not identify the active isomer or prove human mucosal healing. Evidence access: Primary abstract Dietary conjugated linoleic acid activates PPARγ and the intestinal trefoil factor in SW480 cells and mice with dextran sulfate sodium-induced colitis. · 2012 · https://pubmed.ncbi.nlm.nih.gov/23077197/ · DOI 10.3945/jn.112.163931