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Study · Animal study (in vivo) · mouse · 2023

8 results

Iron scavenging and suppression of collagen cross-linking underlie antifibrotic effects of carnosine in the heart with obesity.

Berdaweel IA, Monroe TB, Alowaisi AA, Mahoney JC, Liang IC, Berns KA, Gao D, McLendon JM, Anderson EJ

Frontiers in pharmacology3 Jan 2024Cited by 6 (Europe PMC)

PMID38348353 (opens in a new tab)PMCIDPMC10859874 (opens in a new tab)DOI10.3389/fphar.2023.1275388 (opens in a new tab)PepBankPUB-38348353
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Summary

Oral consumption of histidyl dipeptides such as l-carnosine has been suggested to promote cardiometabolic health, although therapeutic mechanisms remain incompletely understood. We recently reported that oral consumption of a carnosine analog suppressed markers of fibrosis in liver of obese mice, but whether antifibrotic effects of carnosine extend to the heart is not known, nor are the mechanisms by which carnosine is acting. Here, we investigated whether oral carnosine was able to mitigate the adverse cardiac remodeling associated with diet induced obesity in a mouse model of enhanced lipid peroxidation (i.e., glutathione peroxidase 4 deficient mice, GPx4+/-), a model which mimics many of the pathophysiological aspects of metabolic syndrome and T2 diabetes in humans. Wild-type (WT) and GPx4+/-male mice were randomly fed a standard (CNTL) or high fat high sucrose diet (HFHS) for 16 weeks. Seven weeks after starting the diet, a subset of the HFHS mice received carnosine (80 mM) in their drinking water for duration of the study. Carnosine treatment led to a moderate improvement in glycemic control in WT and GPx4+/-mice on HFHS diet, although insulin sensitivity was not significantly affected. Interestingly, while our transcriptomic analysis revealed that carnosine therapy had only modest impact on global gene expression in the heart, carnosine substantially upregulated cardiac GPx4 expression in both WT and GPx4+/-mice on HFHS diet. Carnosine also significantly reduced protein carbonyls and iron levels in myocardial tissue from both genotypes on HFHS diet. Importantly, we observed a robust antifibrotic effect of carnosine therapy in hearts from mice on HFHS diet, which further in vitro experiments suggest is due to carnosine's ability to suppress collagen-cross-linking. Collectively, this study reveals antifibrotic potential of carnosine in the heart with obesity and illustrates key mechanisms by which it may be acting.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study8

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

  1. 01AnimalAnimal study (in vivo)Efficacy outcome

    In WT and GPx4-deficient mice on HFHS diet, carnosine moderately improved glycemic control.

    In plain wordsIn mice on HFHS diet, carnosine moderately improved blood sugar control.

    Peptide
    L-carnosine
    Outcome
    IncreaseGlycemic control
    Study

    mousen: not reported in source

    WT and GPx4-deficient mice on HFHS diet
    Outcome group
    Glycemic control · Metabolic and weight
    Studied dose
    80 mM · oralAs given in this study (mouse).

    Source sentences

    Summary
    Carnosine treatment led to a moderate improvement in glycemic control in WT and GPx4+/-mice on HFHS diet, although insulin sensitivity was not significantly affected.
    2 context sentences
    Summary · context
    Wild-type (WT) and GPx4+/-male mice were randomly fed a standard (CNTL) or high fat high sucrose diet (HFHS) for 16 weeks.
    Summary · context
    Seven weeks after starting the diet, a subset of the HFHS mice received carnosine (80 mM) in their drinking water for duration of the study.
  2. 02AnimalAnimal study (in vivo)Efficacy outcome

    In WT and GPx4-deficient mice on HFHS diet, carnosine did not significantly affect insulin sensitivity.

    In plain wordsIn mice on HFHS diet, carnosine did not significantly affect insulin sensitivity.

    Peptide
    L-carnosine
    Outcome
    No significant changeInsulin sensitivity
    Study

    mousen: not reported in source

    WT and GPx4-deficient mice on HFHS diet
    Outcome group
    Glycemic control · Metabolic and weight
    Studied dose
    80 mM · oralAs given in this study (mouse).

    Source sentences

    Summary
    Carnosine treatment led to a moderate improvement in glycemic control in WT and GPx4+/-mice on HFHS diet, although insulin sensitivity was not significantly affected.
    2 context sentences
    Summary · context
    Wild-type (WT) and GPx4+/-male mice were randomly fed a standard (CNTL) or high fat high sucrose diet (HFHS) for 16 weeks.
    Summary · context
    Seven weeks after starting the diet, a subset of the HFHS mice received carnosine (80 mM) in their drinking water for duration of the study.
  3. 03AnimalAnimal study (in vivo)Mechanism

    In mice on HFHS diet, carnosine had only a modest impact on global cardiac gene expression.

    In plain wordsIn mice on HFHS diet, carnosine had only a modest effect on overall heart gene expression.

    Peptide
    L-carnosine
    Outcome
    Direction not reportedGlobal cardiac gene expression
    Study

    mousen: not reported in source

    WT and GPx4-deficient mice on HFHS diet
    Outcome group
    Receptor activity and mechanism · Cardiovascular
    Studied dose
    80 mM · oralAs given in this study (mouse).

    Source sentences

    Summary
    Interestingly, while our transcriptomic analysis revealed that carnosine therapy had only modest impact on global gene expression in the heart, carnosine substantially upregulated cardiac GPx4 expression in both WT and GPx4+/-mice on HFHS diet.
    2 context sentences
    Summary · context
    Wild-type (WT) and GPx4+/-male mice were randomly fed a standard (CNTL) or high fat high sucrose diet (HFHS) for 16 weeks.
    Summary · context
    Seven weeks after starting the diet, a subset of the HFHS mice received carnosine (80 mM) in their drinking water for duration of the study.
  4. 04AnimalAnimal study (in vivo)Mechanism

    In WT and GPx4-deficient mice on HFHS diet, carnosine increased cardiac GPx4 expression.

    In plain wordsIn mice on HFHS diet, carnosine increased GPx4 expression in the heart.

    Peptide
    L-carnosine
    Outcome
    IncreaseCardiac GPx4 expression
    Study

    mousen: not reported in source

    WT and GPx4-deficient mice on HFHS diet
    Outcome group
    Receptor activity and mechanism · Cardiovascular
    Studied dose
    80 mM · oralAs given in this study (mouse).

    Source sentences

    Summary
    Interestingly, while our transcriptomic analysis revealed that carnosine therapy had only modest impact on global gene expression in the heart, carnosine substantially upregulated cardiac GPx4 expression in both WT and GPx4+/-mice on HFHS diet.
    2 context sentences
    Summary · context
    Wild-type (WT) and GPx4+/-male mice were randomly fed a standard (CNTL) or high fat high sucrose diet (HFHS) for 16 weeks.
    Summary · context
    Seven weeks after starting the diet, a subset of the HFHS mice received carnosine (80 mM) in their drinking water for duration of the study.
  5. 05AnimalAnimal study (in vivo)Mechanism

    In both mouse genotypes on HFHS diet, carnosine significantly reduced myocardial protein carbonyls.

    In plain wordsIn mice on HFHS diet, carnosine reduced protein carbonyls in heart tissue.

    Peptide
    L-carnosine
    Outcome
    DecreaseMyocardial protein carbonyls
    Study

    mousen: not reported in source

    WT and GPx4-deficient mice on HFHS diet
    Outcome group
    Oxidative stress · Cardiovascular
    Studied dose
    80 mM · oralAs given in this study (mouse).

    Source sentences

    Summary
    Carnosine also significantly reduced protein carbonyls and iron levels in myocardial tissue from both genotypes on HFHS diet.
    2 context sentences
    Summary · context
    Wild-type (WT) and GPx4+/-male mice were randomly fed a standard (CNTL) or high fat high sucrose diet (HFHS) for 16 weeks.
    Summary · context
    Seven weeks after starting the diet, a subset of the HFHS mice received carnosine (80 mM) in their drinking water for duration of the study.
  6. 06AnimalAnimal study (in vivo)Mechanism

    In both mouse genotypes on HFHS diet, carnosine significantly reduced myocardial iron levels.

    In plain wordsIn mice on HFHS diet, carnosine reduced iron levels in heart tissue.

    Peptide
    L-carnosine
    Outcome
    DecreaseMyocardial iron
    Study

    mousen: not reported in source

    WT and GPx4-deficient mice on HFHS diet
    Outcome group
    Metabolic pathways and metabolomics · Cardiovascular
    Studied dose
    80 mM · oralAs given in this study (mouse).

    Source sentences

    Summary
    Carnosine also significantly reduced protein carbonyls and iron levels in myocardial tissue from both genotypes on HFHS diet.
    2 context sentences
    Summary · context
    Wild-type (WT) and GPx4+/-male mice were randomly fed a standard (CNTL) or high fat high sucrose diet (HFHS) for 16 weeks.
    Summary · context
    Seven weeks after starting the diet, a subset of the HFHS mice received carnosine (80 mM) in their drinking water for duration of the study.
  7. 07AnimalAnimal study (in vivo)Efficacy outcome

    In mice on HFHS diet, carnosine had a robust antifibrotic effect in the heart.

    In plain wordsIn mice on HFHS diet, carnosine reduced heart fibrosis.

    Peptide
    L-carnosine
    Outcome
    DecreaseCardiac fibrosis
    Study

    mousen: not reported in source

    WT and GPx4-deficient mice on HFHS diet
    Outcome group
    Heart function · Cardiovascular
    Studied dose
    80 mM · oralAs given in this study (mouse).

    Source sentences

    Summary
    Importantly, we observed a robust antifibrotic effect of carnosine therapy in hearts from mice on HFHS diet, which further in vitro experiments suggest is due to carnosine's ability to suppress collagen-cross-linking.
    2 context sentences
    Summary · context
    Wild-type (WT) and GPx4+/-male mice were randomly fed a standard (CNTL) or high fat high sucrose diet (HFHS) for 16 weeks.
    Summary · context
    Seven weeks after starting the diet, a subset of the HFHS mice received carnosine (80 mM) in their drinking water for duration of the study.
  8. 08LabIn vitro (cell-free)Mechanism

    In vitro experiments suggested that carnosine suppressed collagen cross-linking.

    In plain wordsIn lab tests, carnosine appeared to suppress collagen cross-linking.

    Peptide
    L-carnosine
    Outcome
    DecreaseCollagen cross-linking
    Study

    n: not reported in source

    Outcome group
    Receptor activity and mechanism · Cardiovascular
    Studied dose
    Dose not stated

    Source sentences

    Summary
    which further in vitro experiments suggest is due to carnosine's ability to suppress collagen-cross-linking.

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

    27 Oct 2026, 18:20 UTC

    Study results updated

  2. Version 1

    27 Oct 2026, 16:32 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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