Mouse PGC-1alpha / Ppargc1a

evidence_span

{"source_cache": "artifacts/chlorogenic_acid-research/41862684.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7246caa586cbd35b79fa9518b522dc7c1d330aad71c98611ae7cc763f7952644", "start_char": 0, "end_char": 1292, "text_sha256": "7246caa586cbd35b79fa9518b522dc7c1d330aad71c98611ae7cc763f7952644"}

experimental_model

Mouse hepatectomy, genetic tests and Keap1-binding investigation

exposure

CGA treatment; doses not provided in indexed abstract

limitations

Surgical mouse regeneration is not chronic human fatty-liver treatment. Arg415 binding was reported but the abstract does not identify the species of every recombinant construct; no human KEAP1 residue-specific edge is inferred.

nutrient_topic

Chlorogenic acid research collection; topical membership is not evidence of a direct dietary effect. · Chlorogenic acid / 5-O-caffeoylquinic acid

organism

Mus musculus; binding preparation species not resolved from abstract

plain_language

The energy branch is distinct from the cell-cycle branch.

primary_references

[chlorogenic_acid-p41862684] Chlorogenic acid promotes liver regeneration after partial hepatectomy through activating Nrf2 via directly targeting Keap1. (2026). https://pubmed.ncbi.nlm.nih.gov/41862684/ DOI: 10.1038/s41401-026-01770-4

tissue_or_cell_type

Regenerating liver after 70% or 90% partial hepatectomy

Chlorogenic acid: metabolism, signaling and nutrient connections (2026-09-17) · lines 594–605

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mouse hepatectomy, genetic tests and Keap1-binding investigation · source_derived_draft · unverified_draft

### chlorogenic_acid-pgc1-atp PGC-1alpha induction was linked to greater ATP production supporting regeneration. Condition category: normal nutrient_topic: Chlorogenic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: The energy branch is distinct from the cell-cycle branch. organism: Mus musculus; binding preparation species not resolved from abstract tissue_or_cell_type: Regenerating liver after 70% or 90% partial hepatectomy experimental_model: Mouse hepatectomy, genetic tests and Keap1-binding investigation limitations: Surgical mouse regeneration is not chronic human fatty-liver treatment. Arg415 binding was reported but the abstract does not identify the species of every recombinant construct; no human KEAP1 residue-specific edge is inferred. exposure: CGA treatment; doses not provided in indexed abstract evidence_span: {"source_cache": "artifacts/chlorogenic_acid-research/41862684.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7246caa586cbd35b79fa9518b522dc7c1d330aad71c98611ae7cc763f7952644", "start_char": 0, "end_char": 1292, "text_sha256": "7246caa586cbd35b79fa9518b522dc7c1d330aad71c98611ae7cc763f7952644"} [chlorogenic_acid-p41862684] Chlorogenic acid promotes liver regeneration after partial hepatectomy through activating Nrf2 via directly targeting Keap1. (2026). https://pubmed.ncbi.nlm.nih.gov/41862684/ DOI: 10.1038/s41401-026-01770-4

evidence_access

Publisher abstract/introduction plus the authors' article and supplementary legends reproduced in an indexed document. This is source-derived extraction, not raw-data verification. Main-text OCR corrupts some micro-unit symbols; ambiguous doses and binding constants are deliberately not transcribed.

experimental_condition

wild-type mice muscle overexpression · Mouse PGC-1alpha / Ppargc1a Condition belongs to the full experimental contrast; do not separate a joint intervention.

experimental_contrast

{"intervention": "muscle-specific PGC-1alpha overexpression", "comparator": "wild-type mice", "endpoint": "whole-muscle ergothioneine concentration", "effect_direction": "increase", "combination": "single", "conditions": [{"entity_slug": "mouse-ppargc1a", "state": "muscle overexpression"}]} Explicit extracted experimental comparison; source-derived draft.

experimental_model

MCK-PGC-1alpha mice; whole gastrocnemius metabolomics.

interpretation_status

Source-derived research curation; not independent raw-data verification.

limitations

Whole-muscle concentration is not the isolated mitochondrial pool. This does not establish that transporter upregulation is the only causal route.

nutrient_topic

Ergothioneine mitochondrial supplement; shared molecular requirements are not demonstrated dietary interactions. · L-Ergothioneine

plain_language

The muscle pool changed alongside transporter expression.

primary_references

Sprenger et al. Ergothioneine controls mitochondrial function and exercise performance via direct activation of MPST. DOI 10.1016/j.cmet.2025.01.024; PMID 39965563; https://pubmed.ncbi.nlm.nih.gov/39965563/

source_locator

Figure 2F

Ergothioneine: mitochondrial transport, MPST and sulfur-handling dependencies (2026-10-02) · lines 105–105

Original AI-assisted curation of five primary studies with publication identifiers, experimental locators and access limitations. Additive chapter supplement, not publisher full text. · supports · MCK-PGC-1alpha mice; whole gastrocnemius metabolomics. · source_derived_draft · unverified_draft

PGC-1alpha-overexpressing mouse muscle contained more ergothioneine than control muscle.

evidence_access

Publisher abstract/introduction plus the authors' article and supplementary legends reproduced in an indexed document. This is source-derived extraction, not raw-data verification. Main-text OCR corrupts some micro-unit symbols; ambiguous doses and binding constants are deliberately not transcribed.

experimental_condition

wild-type mice muscle overexpression · Mouse PGC-1alpha / Ppargc1a Condition belongs to the full experimental contrast; do not separate a joint intervention.

experimental_contrast

{"intervention": "muscle-specific PGC-1alpha overexpression", "comparator": "wild-type mice", "endpoint": "Slc22a4 mRNA and protein", "effect_direction": "increase", "combination": "single", "conditions": [{"entity_slug": "mouse-ppargc1a", "state": "muscle overexpression"}]} Explicit extracted experimental comparison; source-derived draft.

experimental_model

MCK-PGC-1alpha mice, gastrocnemius muscle, versus wild-type controls.

interpretation_status

Source-derived research curation; not independent raw-data verification.

limitations

Overexpression differs from physiological exercise and human diet; increased transporter abundance is not itself a measured transport flux.

nutrient_topic

Ergothioneine mitochondrial supplement; shared molecular requirements are not demonstrated dietary interactions. · L-Ergothioneine

plain_language

A regulatory programme can alter transporter abundance.

primary_references

Sprenger et al. Ergothioneine controls mitochondrial function and exercise performance via direct activation of MPST. DOI 10.1016/j.cmet.2025.01.024; PMID 39965563; https://pubmed.ncbi.nlm.nih.gov/39965563/

source_locator

Figure 2D-E

Ergothioneine: mitochondrial transport, MPST and sulfur-handling dependencies (2026-10-02) · lines 97–97

Original AI-assisted curation of five primary studies with publication identifiers, experimental locators and access limitations. Additive chapter supplement, not publisher full text. · supports · MCK-PGC-1alpha mice, gastrocnemius muscle, versus wild-type controls. · source_derived_draft · unverified_draft

Muscle PGC-1alpha overexpression increased Slc22a4 mRNA and protein in mice.

evidence_span

{"source_cache": "artifacts/chlorogenic_acid-research/41862684.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7246caa586cbd35b79fa9518b522dc7c1d330aad71c98611ae7cc763f7952644", "start_char": 0, "end_char": 1292, "text_sha256": "7246caa586cbd35b79fa9518b522dc7c1d330aad71c98611ae7cc763f7952644"}

experimental_model

Mouse hepatectomy, genetic tests and Keap1-binding investigation

exposure

CGA treatment; doses not provided in indexed abstract

limitations

Surgical mouse regeneration is not chronic human fatty-liver treatment. Arg415 binding was reported but the abstract does not identify the species of every recombinant construct; no human KEAP1 residue-specific edge is inferred.

nutrient_topic

Chlorogenic acid research collection; topical membership is not evidence of a direct dietary effect. · Chlorogenic acid / 5-O-caffeoylquinic acid

organism

Mus musculus; binding preparation species not resolved from abstract

plain_language

A second branch connects the response to energy metabolism.

primary_references

[chlorogenic_acid-p41862684] Chlorogenic acid promotes liver regeneration after partial hepatectomy through activating Nrf2 via directly targeting Keap1. (2026). https://pubmed.ncbi.nlm.nih.gov/41862684/ DOI: 10.1038/s41401-026-01770-4

tissue_or_cell_type

Regenerating liver after 70% or 90% partial hepatectomy

Chlorogenic acid: metabolism, signaling and nutrient connections (2026-09-17) · lines 581–592

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mouse hepatectomy, genetic tests and Keap1-binding investigation · source_derived_draft · unverified_draft

### chlorogenic_acid-nrf2-pgc1 Nrf2 activation increased PGC-1alpha mRNA in the regeneration model. Condition category: normal nutrient_topic: Chlorogenic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: A second branch connects the response to energy metabolism. organism: Mus musculus; binding preparation species not resolved from abstract tissue_or_cell_type: Regenerating liver after 70% or 90% partial hepatectomy experimental_model: Mouse hepatectomy, genetic tests and Keap1-binding investigation limitations: Surgical mouse regeneration is not chronic human fatty-liver treatment. Arg415 binding was reported but the abstract does not identify the species of every recombinant construct; no human KEAP1 residue-specific edge is inferred. exposure: CGA treatment; doses not provided in indexed abstract evidence_span: {"source_cache": "artifacts/chlorogenic_acid-research/41862684.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7246caa586cbd35b79fa9518b522dc7c1d330aad71c98611ae7cc763f7952644", "start_char": 0, "end_char": 1292, "text_sha256": "7246caa586cbd35b79fa9518b522dc7c1d330aad71c98611ae7cc763f7952644"} [chlorogenic_acid-p41862684] Chlorogenic acid promotes liver regeneration after partial hepatectomy through activating Nrf2 via directly targeting Keap1. (2026). https://pubmed.ncbi.nlm.nih.gov/41862684/ DOI: 10.1038/s41401-026-01770-4

evidence_access

Primary abstract

experimental_model

Mouse feeding and exercise experiment.

limitations

Expression alone does not establish necessity of PGC-1alpha or predict a human exercise response.

nutrient_topic

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

plain_language

The muscle expressed more components associated with mitochondrial capacity.

primary_references

The astaxanthin-induced improvement in lipid metabolism during exercise is mediated by a PGC-1α increase in skeletal muscle. · 2014 · https://pubmed.ncbi.nlm.nih.gov/24688216/ · DOI 10.3164/jcbn.13-110

Astaxanthin: transport, membrane chemistry, 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 · Mouse feeding and exercise experiment. · source_derived_draft · unverified_draft

## astaxanthin-pgc1a-expression The muscle expressed more components associated with mitochondrial capacity. Two weeks of astaxanthin feeding increased PGC-1alpha and downstream mitochondrial proteins in exercised mouse muscle. Model: Mouse feeding and exercise experiment. Limitations: Expression alone does not establish necessity of PGC-1alpha or predict a human exercise response. Evidence access: Primary abstract The astaxanthin-induced improvement in lipid metabolism during exercise is mediated by a PGC-1α increase in skeletal muscle. · 2014 · https://pubmed.ncbi.nlm.nih.gov/24688216/ · DOI 10.3164/jcbn.13-110

evidence_access

Primary abstract

experimental_model

High-fat-fed C57BL/6J mice.

limitations

Five percent of diet is not a human supplement dose; this study did not observe reduced food intake.

nutrient_topic

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

plain_language

A high dietary exposure changed energy expenditure in mice.

primary_references

Butyrate improves insulin sensitivity and increases energy expenditure in mice. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19366864/ · DOI 10.2337/db08-1637

Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 550–556

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · High-fat-fed C57BL/6J mice. · source_derived_draft · unverified_draft

## butyrate-mouse-thermogenesis A high dietary exposure changed energy expenditure in mice. Feeding sodium butyrate at 5% of a high-fat diet increased thermogenesis and mitochondrial adaptation in mouse muscle and brown fat, with increased PGC-1alpha expression and insulin sensitivity. Model: High-fat-fed C57BL/6J mice. Limitations: Five percent of diet is not a human supplement dose; this study did not observe reduced food intake. Evidence access: Primary abstract Butyrate improves insulin sensitivity and increases energy expenditure in mice. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19366864/ · DOI 10.2337/db08-1637

evidence_access

Primary abstract

experimental_model

High-fat-diet C57BL/6 mice; related mouse FL83B hepatocyte experiments also reported.

limitations

The paper describes agonist activity; the accessed abstract does not resolve direct receptor affinity or establish a human clinical effect.

nutrient_topic

Red yeast rice collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Red yeast rice

plain_language

A transcriptional program provides a distinct route from statin inhibition.

primary_references

[24275089] Monascin and ankaflavin act as natural AMPK activators with PPARα agonist activity to down-regulate nonalcoholic steatohepatitis in high-fat diet-fed C57BL/6 mice. · 2014 · https://pubmed.ncbi.nlm.nih.gov/24275089/ · DOI 10.1016/j.fct.2013.11.015

Red yeast rice: constituents, mevalonate, CoQ and product-specific interactions (2026-09-20) · lines 228–234

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · High-fat-diet C57BL/6 mice; related mouse FL83B hepatocyte experiments also reported. · source_derived_draft · unverified_draft

## red-yeast-rice-ankaflavin-ppara A transcriptional program provides a distinct route from statin inhibition. Ankaflavin increased hepatic PPAR-alpha expression and promoted a fatty-acid-oxidation program in the mouse study. Model: High-fat-diet C57BL/6 mice; related mouse FL83B hepatocyte experiments also reported. Limitations: The paper describes agonist activity; the accessed abstract does not resolve direct receptor affinity or establish a human clinical effect. Evidence access: Primary abstract [24275089] Monascin and ankaflavin act as natural AMPK activators with PPARα agonist activity to down-regulate nonalcoholic steatohepatitis in high-fat diet-fed C57BL/6 mice. · 2014 · https://pubmed.ncbi.nlm.nih.gov/24275089/ · DOI 10.1016/j.fct.2013.11.015

evidence_access

Primary abstract

experimental_model

High-fat-diet C57BL/6 mice; related mouse FL83B hepatocyte experiments also reported.

limitations

The paper describes agonist activity; the accessed abstract does not resolve direct receptor affinity or establish a human clinical effect.

nutrient_topic

Red yeast rice collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Red yeast rice

plain_language

A transcriptional program provides a distinct route from statin inhibition.

primary_references

[24275089] Monascin and ankaflavin act as natural AMPK activators with PPARα agonist activity to down-regulate nonalcoholic steatohepatitis in high-fat diet-fed C57BL/6 mice. · 2014 · https://pubmed.ncbi.nlm.nih.gov/24275089/ · DOI 10.1016/j.fct.2013.11.015

Red yeast rice: constituents, mevalonate, CoQ and product-specific interactions (2026-09-20) · lines 212–218

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · High-fat-diet C57BL/6 mice; related mouse FL83B hepatocyte experiments also reported. · source_derived_draft · unverified_draft

## red-yeast-rice-monascin-ppara A transcriptional program provides a distinct route from statin inhibition. Monascin increased hepatic PPAR-alpha expression and promoted a fatty-acid-oxidation program in the mouse study. Model: High-fat-diet C57BL/6 mice; related mouse FL83B hepatocyte experiments also reported. Limitations: The paper describes agonist activity; the accessed abstract does not resolve direct receptor affinity or establish a human clinical effect. Evidence access: Primary abstract [24275089] Monascin and ankaflavin act as natural AMPK activators with PPARα agonist activity to down-regulate nonalcoholic steatohepatitis in high-fat diet-fed C57BL/6 mice. · 2014 · https://pubmed.ncbi.nlm.nih.gov/24275089/ · DOI 10.1016/j.fct.2013.11.015

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text, RNA interference methods and Figure 7

experimental_model

Mouse C2C12 cells; AMPK-alpha1/2 siRNA, astaxanthin 50 micromolar.

limitations

Dual-subunit depletion cannot identify one subunit as sufficient; culture exposure is not an oral dose.

nutrient_topic

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

plain_language

The mitochondrial response depended on intact energy-sensing machinery.

primary_references

Astaxanthin stimulates mitochondrial biogenesis in insulin resistant muscle via activation of AMPK pathway. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32003547/ · DOI 10.1002/jcsm.12530

trigger_kind

machinery_impairment Imported condition classification; unverified.

Astaxanthin: transport, membrane chemistry, signaling and nutrient interactions (2026-09-19) · lines 334–340

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Mouse C2C12 cells; AMPK-alpha1/2 siRNA, astaxanthin 50 micromolar. · source_derived_draft · unverified_draft

## astaxanthin-ampk-loss The mitochondrial response depended on intact energy-sensing machinery. Combined AMPK-alpha1/alpha2 siRNA depletion in C2C12 cells abolished the mitochondrial-biogenesis response to astaxanthin. Model: Mouse C2C12 cells; AMPK-alpha1/2 siRNA, astaxanthin 50 micromolar. Limitations: Dual-subunit depletion cannot identify one subunit as sufficient; culture exposure is not an oral dose. Evidence access: Primary full text, RNA interference methods and Figure 7 Astaxanthin stimulates mitochondrial biogenesis in insulin resistant muscle via activation of AMPK pathway. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32003547/ · DOI 10.1002/jcsm.12530

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