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Study · Animal study (in vivo) · mouse · 2017

11 results

AICAR ameliorates high-fat diet-associated pathophysiology in mouse and ex vivo models, independent of adiponectin.

Börgeson E, Wallenius V, Syed GH, Darshi M, Lantero Rodriguez J, Biörserud C, Ragnmark Ek M, Björklund P, Quiding-Järbrink M, Fändriks L, Godson C, Sharma K

Diabetologia10 Feb 2017Cited by 26 (Europe PMC)

PMID28188334 (opens in a new tab)PMCIDPMC6518112 (opens in a new tab)DOI10.1007/s00125-017-4211-9 (opens in a new tab)PepBankPUB-28188334
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Summary

Aims/hypothesisIn this study, we aimed to evaluate the therapeutic potential of 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), an activator of AMP-activated protein kinase, for ameliorating high-fat diet (HFD)-induced pathophysiology in mice. We also aimed to determine whether the beneficial effects of AICAR were dependent on adiponectin. Furthermore, human adipose tissue was used to examine the effect of AICAR ex vivo.MethodsSix-week-old male C57BL/6J wild-type and Adipoq -/- mice were fed a standard-fat diet (10% fat) or an HFD (60% fat) for 12 weeks and given vehicle or AICAR (500 μg/g) three times/week from weeks 4-12. Diet-induced pathophysiology was examined in mice after 11 weeks by IPGTT and after 12 weeks by flow cytometry and western blotting. Human adipose tissue biopsies from obese (BMI 35-50 kg/m2) individuals were incubated with vehicle or AICAR (1 mmol/l) for 6 h at 37°C, after which inflammation was characterised by ELISA (TNF-α) and flow cytometry.ResultsAICAR attenuated adipose inflammation in mice fed an HFD, promoting an M1-to-M2 macrophage phenotype switch, while reducing infiltration of CD8+ T cells. AICAR treatment of mice fed an HFD partially restored glucose tolerance and attenuated hepatic steatosis and kidney disease, as evidenced by reduced albuminuria (p 2O2 (p -/- mice. AICAR-mediated protection occurred independently of adiponectin, as similar protection was observed in wild-type and Adipoq -/- mice. In addition, AICAR promoted an M1-to-M2 macrophage phenotype switch and reduced TNF-α production in tissue explants from obese human patients.Conclusions/interpretationAICAR may promote metabolic health and protect against obesity-induced systemic diseases in an adiponectin-independent manner. Furthermore, AICAR reduced inflammation in human adipose tissue explants, suggesting by proof-of-principle that the drug may reduce obesity-induced complications in humans.Trial registrationClinicalTrials.gov NCT02322073.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study11

10 results from studies that gave the peptide. No result from this study comes from people.

  1. 01AnimalAnimal study (in vivo)Efficacy outcome

    In high-fat-fed mice, AICAR attenuated adipose inflammation.

    In plain wordsIn mice fed a high-fat diet, AICAR reduced fat tissue inflammation compared with vehicle.

    Peptide
    AICAR (acadesine)
    Outcome
    DecreaseAdipose inflammation
    Study

    mousen: not reported in source

    High-fat-diet wild-type and Adipoq knockout mice
    Comparator
    Vehicle
    Outcome group
    Inflammation markers · Immune and inflammation
    Studied dose
    500 μg/g three times/week · weeks 4-12As given in this study (mouse).

    Source sentences

    Summary
    AICAR attenuated adipose inflammation in mice fed an HFD, promoting an M1-to-M2 macrophage phenotype switch, while reducing infiltration of CD8+ T cells.
    1 context sentence
    Summary · context
    Six-week-old male C57BL/6J wild-type and Adipoq -/- mice were fed a standard-fat diet (10% fat) or an HFD (60% fat) for 12 weeks and given vehicle or AICAR (500 μg/g) three times/week from weeks 4-12.
  2. 02AnimalAnimal study (in vivo)Efficacy outcome

    In high-fat-fed mice, AICAR promoted an M1-to-M2 macrophage phenotype switch.

    In plain wordsIn mice fed a high-fat diet, AICAR increased the macrophage switch from M1 to M2 compared with vehicle.

    Peptide
    AICAR (acadesine)
    Outcome
    IncreaseMacrophage phenotype switch
    Study

    mousen: not reported in source

    High-fat-diet wild-type and Adipoq knockout mice
    Comparator
    Vehicle
    Outcome group
    Immune response · Immune and inflammation
    Studied dose
    500 μg/g three times/week · weeks 4-12As given in this study (mouse).

    Source sentences

    Summary
    AICAR attenuated adipose inflammation in mice fed an HFD, promoting an M1-to-M2 macrophage phenotype switch, while reducing infiltration of CD8+ T cells.
    1 context sentence
    Summary · context
    Six-week-old male C57BL/6J wild-type and Adipoq -/- mice were fed a standard-fat diet (10% fat) or an HFD (60% fat) for 12 weeks and given vehicle or AICAR (500 μg/g) three times/week from weeks 4-12.
  3. 03AnimalAnimal study (in vivo)Efficacy outcome

    In high-fat-fed mice, AICAR reduced adipose CD8-positive T-cell infiltration.

    In plain wordsIn mice fed a high-fat diet, AICAR reduced CD8 T-cell entry into fat tissue compared with vehicle.

    Peptide
    AICAR (acadesine)
    Outcome
    DecreaseCD8 T-cell infiltration
    Study

    mousen: not reported in source

    High-fat-diet wild-type and Adipoq knockout mice
    Comparator
    Vehicle
    Outcome group
    Immune response · Immune and inflammation
    Studied dose
    500 μg/g three times/week · weeks 4-12As given in this study (mouse).

    Source sentences

    Summary
    AICAR attenuated adipose inflammation in mice fed an HFD, promoting an M1-to-M2 macrophage phenotype switch, while reducing infiltration of CD8+ T cells.
    1 context sentence
    Summary · context
    Six-week-old male C57BL/6J wild-type and Adipoq -/- mice were fed a standard-fat diet (10% fat) or an HFD (60% fat) for 12 weeks and given vehicle or AICAR (500 μg/g) three times/week from weeks 4-12.
  4. 04AnimalAnimal study (in vivo)Efficacy outcome

    In high-fat-fed mice, AICAR partially restored glucose tolerance.

    In plain wordsIn mice fed a high-fat diet, AICAR partly improved glucose tolerance compared with vehicle.

    Peptide
    AICAR (acadesine)
    Outcome
    IncreaseGlucose tolerance
    Study

    mousen: not reported in source

    High-fat-diet wild-type and Adipoq knockout mice
    Comparator
    Vehicle
    Outcome group
    Glycemic control · Metabolic and weight
    Studied dose
    500 μg/g three times/week · weeks 4-12As given in this study (mouse).

    Source sentences

    Summary
    AICAR treatment of mice fed an HFD partially restored glucose tolerance and attenuated hepatic steatosis and kidney disease, as evidenced by reduced albuminuria (p 2O2 (p -/- mice.
    1 context sentence
    Summary · context
    Six-week-old male C57BL/6J wild-type and Adipoq -/- mice were fed a standard-fat diet (10% fat) or an HFD (60% fat) for 12 weeks and given vehicle or AICAR (500 μg/g) three times/week from weeks 4-12.
  5. 05AnimalAnimal study (in vivo)Efficacy outcome

    In high-fat-fed mice, AICAR attenuated hepatic steatosis.

    In plain wordsIn mice fed a high-fat diet, AICAR reduced fatty liver compared with vehicle.

    Peptide
    AICAR (acadesine)
    Outcome
    DecreaseHepatic steatosis
    Study

    mousen: not reported in source

    High-fat-diet wild-type and Adipoq knockout mice
    Comparator
    Vehicle
    Outcome group
    Liver fat and liver function · Liver
    Studied dose
    500 μg/g three times/week · weeks 4-12As given in this study (mouse).

    Source sentences

    Summary
    AICAR treatment of mice fed an HFD partially restored glucose tolerance and attenuated hepatic steatosis and kidney disease, as evidenced by reduced albuminuria (p 2O2 (p -/- mice.
    1 context sentence
    Summary · context
    Six-week-old male C57BL/6J wild-type and Adipoq -/- mice were fed a standard-fat diet (10% fat) or an HFD (60% fat) for 12 weeks and given vehicle or AICAR (500 μg/g) three times/week from weeks 4-12.
  6. 06AnimalAnimal study (in vivo)Efficacy outcome

    In high-fat-fed wild-type and adiponectin-deficient mice, AICAR reduced albuminuria.

    In plain wordsIn mice fed a high-fat diet, AICAR reduced urinary albumin compared with vehicle, with or without adiponectin.

    Peptide
    AICAR (acadesine)
    Outcome
    DecreaseAlbuminuria
    Study

    mousen: not reported in source

    High-fat-diet wild-type and Adipoq knockout mice
    Comparator
    Vehicle
    Outcome group
    Kidney function · Kidney and urinary
    Studied dose
    500 μg/g three times/week · weeks 4-12As given in this study (mouse).

    Source sentences

    Summary
    AICAR treatment of mice fed an HFD partially restored glucose tolerance and attenuated hepatic steatosis and kidney disease, as evidenced by reduced albuminuria (p 2O2 (p -/- mice.
    1 context sentence
    Summary · context
    Six-week-old male C57BL/6J wild-type and Adipoq -/- mice were fed a standard-fat diet (10% fat) or an HFD (60% fat) for 12 weeks and given vehicle or AICAR (500 μg/g) three times/week from weeks 4-12.
  7. 07AnimalAnimal study (in vivo)Efficacy outcome

    In high-fat-fed wild-type and adiponectin-deficient mice, AICAR reduced urinary hydrogen peroxide.

    In plain wordsIn mice fed a high-fat diet, AICAR reduced urinary hydrogen peroxide compared with vehicle, with or without adiponectin.

    Peptide
    AICAR (acadesine)
    Outcome
    DecreaseUrinary hydrogen peroxide
    Study

    mousen: not reported in source

    High-fat-diet wild-type and Adipoq knockout mice
    Comparator
    Vehicle
    Outcome group
    Kidney function · Kidney and urinary
    Studied dose
    500 μg/g three times/week · weeks 4-12As given in this study (mouse).

    Source sentences

    Summary
    AICAR treatment of mice fed an HFD partially restored glucose tolerance and attenuated hepatic steatosis and kidney disease, as evidenced by reduced albuminuria (p 2O2 (p -/- mice.
    1 context sentence
    Summary · context
    Six-week-old male C57BL/6J wild-type and Adipoq -/- mice were fed a standard-fat diet (10% fat) or an HFD (60% fat) for 12 weeks and given vehicle or AICAR (500 μg/g) three times/week from weeks 4-12.
  8. 08AnimalAnimal study (in vivo)Efficacy outcome

    In high-fat-fed wild-type and adiponectin-deficient mice, AICAR reduced renal superoxide levels.

    In plain wordsIn mice fed a high-fat diet, AICAR reduced kidney superoxide compared with vehicle, with or without adiponectin.

    Peptide
    AICAR (acadesine)
    Outcome
    DecreaseRenal superoxide
    Study

    mousen: not reported in source

    High-fat-diet wild-type and Adipoq knockout mice
    Comparator
    Vehicle
    Outcome group
    Kidney function · Kidney and urinary
    Studied dose
    500 μg/g three times/week · weeks 4-12As given in this study (mouse).

    Source sentences

    Summary
    AICAR treatment of mice fed an HFD partially restored glucose tolerance and attenuated hepatic steatosis and kidney disease, as evidenced by reduced albuminuria (p 2O2 (p -/- mice.
    1 context sentence
    Summary · context
    Six-week-old male C57BL/6J wild-type and Adipoq -/- mice were fed a standard-fat diet (10% fat) or an HFD (60% fat) for 12 weeks and given vehicle or AICAR (500 μg/g) three times/week from weeks 4-12.
  9. 09LabEx vivo tissueEfficacy outcome

    In adipose explants from obese humans, AICAR promoted an M1-to-M2 macrophage phenotype switch.

    In plain wordsIn lab tests, AICAR increased the macrophage switch from M1 to M2 in obese human fat tissue compared with vehicle.

    Peptide
    AICAR (acadesine)
    Outcome
    IncreaseMacrophage phenotype switch in human explants
    Study

    humann: not reported in source

    Adipose tissue explants from obese individuals
    Comparator
    Vehicle
    Outcome group
    Immune response · Immune and inflammation
    Studied dose
    1 mmol/l · 6 hAs given in this study (human).

    Source sentences

    Summary
    In addition, AICAR promoted an M1-to-M2 macrophage phenotype switch and reduced TNF-α production in tissue explants from obese human patients.
    1 context sentence
    Summary · context
    Human adipose tissue biopsies from obese (BMI 35-50 kg/m2) individuals were incubated with vehicle or AICAR (1 mmol/l) for 6 h at 37°C, after which inflammation was characterised by ELISA (TNF-α) and flow cytometry.
  10. 10LabEx vivo tissueEfficacy outcome

    In adipose explants from obese humans, AICAR reduced TNF-alpha production.

    In plain wordsIn lab tests, AICAR reduced TNF-alpha production in obese human fat tissue compared with vehicle.

    Peptide
    AICAR (acadesine)
    Outcome
    DecreaseTNF-alpha production in human explants
    Study

    humann: not reported in source

    Adipose tissue explants from obese individuals
    Comparator
    Vehicle
    Outcome group
    Inflammation markers · Immune and inflammation
    Studied dose
    1 mmol/l · 6 hAs given in this study (human).

    Source sentences

    Summary
    In addition, AICAR promoted an M1-to-M2 macrophage phenotype switch and reduced TNF-α production in tissue explants from obese human patients.
    1 context sentence
    Summary · context
    Human adipose tissue biopsies from obese (BMI 35-50 kg/m2) individuals were incubated with vehicle or AICAR (1 mmol/l) for 6 h at 37°C, after which inflammation was characterised by ELISA (TNF-α) and flow cytometry.

Studies that did not test the peptide alone1

In this study, AICAR (acadesine) was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking AICAR (acadesine).

  1. 11AnimalNot a test of AICAR (acadesine) aloneAnimal study (in vivo)Mechanism

    In high-fat-fed mice, AICAR-mediated protection was similar in wild-type and adiponectin-deficient mice.

    In plain wordsIn mice fed a high-fat diet, AICAR protection was similar in mice with and without adiponectin.

    Peptide
    AICAR (acadesine)
    Outcome
    No significant changeAdiponectin dependence of protection
    Study

    mousen: not reported in source

    High-fat-diet wild-type and Adipoq knockout mice
    Comparator
    Wild-type mice treated with AICAR
    Outcome group
    Receptor activity and mechanism · Metabolic and weight

    Source sentences

    Summary
    AICAR-mediated protection occurred independently of adiponectin, as similar protection was observed in wild-type and Adipoq -/- mice.
    1 context sentence
    Summary · context
    Six-week-old male C57BL/6J wild-type and Adipoq -/- mice were fed a standard-fat diet (10% fat) or an HFD (60% fat) for 12 weeks and given vehicle or AICAR (500 μg/g) three times/week from weeks 4-12.

    In this study, AICAR (acadesine) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking AICAR (acadesine).

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Version 2Current

    21 Oct 2026, 15:58 UTC

    Study results updated

  2. Version 1

    21 Oct 2026, 12:50 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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