Component

Experimentally reduced-isoleucine mouse diet

Context-specific entity; species, compartment and exposure are stated on each claim.

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. Starting 67% isoleucine restriction at twenty months improved selected metabolic/frailty measures but reduced grip strength in both sexes and produced mixed sex-dependent cardiac effects.

    Experimentally reduced-isoleucine mouse diet → Functional outcomes of late-life isoleucine restriction source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Aged male and female C57BL/6J.Nia mice.
    limitations
    Not evidence that severe restriction is desirable in older humans; differs from the six-month-start longevity experiment.
    nutrient_topic
    L-Isoleucine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Isoleucine
    plain_language
    A diet can improve some endpoints while worsening others.
    primary_references
    Late-life protein or isoleucine restriction impacts physiological and molecular signatures of aging. · 2024 · https://pubmed.ncbi.nlm.nih.gov/39604703/ · DOI 10.1038/s43587-024-00744-7

    L-Isoleucine: transport, translation, catabolism and cross-nutrient mechanisms (2026-09-19) · lines 426–432

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Aged male and female C57BL/6J.Nia mice. · source_derived_draft · unverified_draft

    ## isoleucine-late-life-tradeoff A diet can improve some endpoints while worsening others. Starting 67% isoleucine restriction at twenty months improved selected metabolic/frailty measures but reduced grip strength in both sexes and produced mixed sex-dependent cardiac effects. Model: Aged male and female C57BL/6J.Nia mice. Limitations: Not evidence that severe restriction is desirable in older humans; differs from the six-month-start longevity experiment. Evidence access: Primary abstract Late-life protein or isoleucine restriction impacts physiological and molecular signatures of aging. · 2024 · https://pubmed.ncbi.nlm.nih.gov/39604703/ · DOI 10.1038/s43587-024-00744-7
    Complete structured claim and evidence

  2. A 67% isoleucine reduction in formulated diets increased glucose infusion requirements and hepatic insulin sensitivity during clamps in mice.

    Experimentally reduced-isoleucine mouse diet → Hepatic insulin response in the low-isoleucine diet study source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary full text
    experimental_model
    Mouse isocaloric amino-acid-defined diets; other amino acids adjusted to maintain amino-acid calories.
    limitations
    Restriction is not complete deprivation; human isolated-isoleucine restriction efficacy was not tested.
    nutrient_topic
    L-Isoleucine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Isoleucine
    plain_language
    Reduced chronic supply changed liver glucose regulation in this dietary context.
    primary_references
    The adverse metabolic effects of branched-chain amino acids are mediated by isoleucine and valine. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33887198/ · DOI 10.1016/j.cmet.2021.03.025

    L-Isoleucine: transport, translation, catabolism and cross-nutrient mechanisms (2026-09-19) · lines 370–376

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse isocaloric amino-acid-defined diets; other amino acids adjusted to maintain amino-acid calories. · source_derived_draft · unverified_draft

    ## isoleucine-restriction-clamp Reduced chronic supply changed liver glucose regulation in this dietary context. A 67% isoleucine reduction in formulated diets increased glucose infusion requirements and hepatic insulin sensitivity during clamps in mice. Model: Mouse isocaloric amino-acid-defined diets; other amino acids adjusted to maintain amino-acid calories. Limitations: Restriction is not complete deprivation; human isolated-isoleucine restriction efficacy was not tested. Evidence access: Primary full text The adverse metabolic effects of branched-chain amino acids are mediated by isoleucine and valine. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33887198/ · DOI 10.1016/j.cmet.2021.03.025
    Complete structured claim and evidence

  3. The reduced-isoleucine diet increased hepatic FGF21 expression and circulating FGF21, with adipose UCP1-associated changes and increased energy expenditure.

    Experimentally reduced-isoleucine mouse diet → Mouse fibroblast growth factor 21 / Fgf21 source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary full text
    experimental_model
    Mouse formulated-diet and tissue studies.
    limitations
    Co-change alone does not show that every metabolic benefit depends on FGF21.
    nutrient_topic
    L-Isoleucine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Isoleucine
    plain_language
    Dietary composition elicited a liver-to-adipose hormonal response.
    primary_references
    The adverse metabolic effects of branched-chain amino acids are mediated by isoleucine and valine. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33887198/ · DOI 10.1016/j.cmet.2021.03.025

    L-Isoleucine: transport, translation, catabolism and cross-nutrient mechanisms (2026-09-19) · lines 378–384

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse formulated-diet and tissue studies. · source_derived_draft · unverified_draft

    ## isoleucine-restriction-fgf21 Dietary composition elicited a liver-to-adipose hormonal response. The reduced-isoleucine diet increased hepatic FGF21 expression and circulating FGF21, with adipose UCP1-associated changes and increased energy expenditure. Model: Mouse formulated-diet and tissue studies. Limitations: Co-change alone does not show that every metabolic benefit depends on FGF21. Evidence access: Primary full text The adverse metabolic effects of branched-chain amino acids are mediated by isoleucine and valine. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33887198/ · DOI 10.1016/j.cmet.2021.03.025
    Complete structured claim and evidence

  4. Liver-specific Gcn2 deletion did not prevent low-isoleucine improvements in glucose tolerance or body-composition measures.

    Experimentally reduced-isoleucine mouse diet → Mouse GCN2 / Eif2ak4 source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary full text
    experimental_model
    Mouse liver-specific Gcn2 knockout, twelve-day and three-week glucose tests.
    limitations
    Not equivalent to complete cellular starvation or loss of GCN2 in every tissue.
    nutrient_topic
    L-Isoleucine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Isoleucine
    plain_language
    A common amino-acid stress sensor was dispensable in this liver/diet experiment.
    primary_references
    The adverse metabolic effects of branched-chain amino acids are mediated by isoleucine and valine. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33887198/ · DOI 10.1016/j.cmet.2021.03.025
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    L-Isoleucine: transport, translation, catabolism and cross-nutrient mechanisms (2026-09-19) · lines 402–408

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse liver-specific Gcn2 knockout, twelve-day and three-week glucose tests. · source_derived_draft · unverified_draft

    ## isoleucine-restriction-gcn2-boundary A common amino-acid stress sensor was dispensable in this liver/diet experiment. Liver-specific Gcn2 deletion did not prevent low-isoleucine improvements in glucose tolerance or body-composition measures. Model: Mouse liver-specific Gcn2 knockout, twelve-day and three-week glucose tests. Limitations: Not equivalent to complete cellular starvation or loss of GCN2 in every tissue. Evidence access: Primary full text The adverse metabolic effects of branched-chain amino acids are mediated by isoleucine and valine. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33887198/ · DOI 10.1016/j.cmet.2021.03.025
    Complete structured claim and evidence

  5. Isoleucine-restricted feeding beginning at six months extended lifespan in male and female genetically heterogeneous UM-HET3 mice, more strongly in males.

    Experimentally reduced-isoleucine mouse diet → Lifespan in the UM-HET3 isoleucine-restriction study source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary full text
    experimental_model
    UM-HET3 mice; 67% dietary isoleucine reduction with controlled diet formulation.
    limitations
    Not a human lifespan finding, and not an independent laboratory replication of all prior Lamming-group diet findings.
    nutrient_topic
    L-Isoleucine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Isoleucine
    plain_language
    A controlled mouse study found an age- and sex-dependent longevity effect.
    primary_references
    Dietary restriction of isoleucine increases healthspan and lifespan of genetically heterogeneous mice. · 2023 · https://pubmed.ncbi.nlm.nih.gov/37939658/ · DOI 10.1016/j.cmet.2023.10.005

    L-Isoleucine: transport, translation, catabolism and cross-nutrient mechanisms (2026-09-19) · lines 418–424

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · UM-HET3 mice; 67% dietary isoleucine reduction with controlled diet formulation. · source_derived_draft · unverified_draft

    ## isoleucine-restriction-lifespan A controlled mouse study found an age- and sex-dependent longevity effect. Isoleucine-restricted feeding beginning at six months extended lifespan in male and female genetically heterogeneous UM-HET3 mice, more strongly in males. Model: UM-HET3 mice; 67% dietary isoleucine reduction with controlled diet formulation. Limitations: Not a human lifespan finding, and not an independent laboratory replication of all prior Lamming-group diet findings. Evidence access: Primary full text Dietary restriction of isoleucine increases healthspan and lifespan of genetically heterogeneous mice. · 2023 · https://pubmed.ncbi.nlm.nih.gov/37939658/ · DOI 10.1016/j.cmet.2023.10.005
    Complete structured claim and evidence

  6. Low isoleucine improved glucose tolerance and body composition despite liver-specific Tsc1 deletion and constitutive hepatic mTORC1 activity.

    Experimentally reduced-isoleucine mouse diet → Constitutive hepatic mTORC1 activity in Tsc1-knockout mice source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary full text
    experimental_model
    Mouse liver-specific Tsc1 knockout and littermate dietary experiments.
    limitations
    Does not exclude mTOR roles in other organs or settings.
    nutrient_topic
    L-Isoleucine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Isoleucine
    plain_language
    Suppressing liver mTORC1 was not necessary for these outcomes.
    primary_references
    The adverse metabolic effects of branched-chain amino acids are mediated by isoleucine and valine. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33887198/ · DOI 10.1016/j.cmet.2021.03.025
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    L-Isoleucine: transport, translation, catabolism and cross-nutrient mechanisms (2026-09-19) · lines 394–400

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse liver-specific Tsc1 knockout and littermate dietary experiments. · source_derived_draft · unverified_draft

    ## isoleucine-restriction-mtor-boundary Suppressing liver mTORC1 was not necessary for these outcomes. Low isoleucine improved glucose tolerance and body composition despite liver-specific Tsc1 deletion and constitutive hepatic mTORC1 activity. Model: Mouse liver-specific Tsc1 knockout and littermate dietary experiments. Limitations: Does not exclude mTOR roles in other organs or settings. Evidence access: Primary full text The adverse metabolic effects of branched-chain amino acids are mediated by isoleucine and valine. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33887198/ · DOI 10.1016/j.cmet.2021.03.025
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. Whole-body Fgf21 deletion blunted low-isoleucine-induced energy expenditure and hyperphagia but did not abolish improved glucose tolerance.

    Mouse fibroblast growth factor 21 / Fgf21 → Energy-expenditure response to low-isoleucine diet source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary full text
    experimental_model
    Fgf21-knockout mice and littermate diet comparisons.
    limitations
    Do not label FGF21 a required mediator of all isoleucine-restriction effects.
    nutrient_topic
    L-Isoleucine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Isoleucine
    plain_language
    Different outcomes used partly different routes.
    primary_references
    The adverse metabolic effects of branched-chain amino acids are mediated by isoleucine and valine. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33887198/ · DOI 10.1016/j.cmet.2021.03.025
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    L-Isoleucine: transport, translation, catabolism and cross-nutrient mechanisms (2026-09-19) · lines 386–392

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Fgf21-knockout mice and littermate diet comparisons. · source_derived_draft · unverified_draft

    ## isoleucine-restriction-fgf21-loss Different outcomes used partly different routes. Whole-body Fgf21 deletion blunted low-isoleucine-induced energy expenditure and hyperphagia but did not abolish improved glucose tolerance. Model: Fgf21-knockout mice and littermate diet comparisons. Limitations: Do not label FGF21 a required mediator of all isoleucine-restriction effects. Evidence access: Primary full text The adverse metabolic effects of branched-chain amino acids are mediated by isoleucine and valine. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33887198/ · DOI 10.1016/j.cmet.2021.03.025
    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.

    Evidence, AI assistance and curation standards