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Study · Animal study (in vivo) · mouse · 2025

8 results

Comparative analysis of LJ-4378 and tirzepatide in mouse models of obesity and weight regain.

Kim H, Kim SW, Choi C, Joo S, Kim G, Kim M, Yang E, Lee J, Chung S, Jeong LS, Lee YH

Archives of pharmacal research7 Nov 2025Cited by 1 (Europe PMC)

PMID41199017 (opens in a new tab)PMCIDPMC12680861 (opens in a new tab)DOI10.1007/s12272-025-01575-9 (opens in a new tab)PepBankPUB-41199017
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Summary

We previously developed LJ-4378, a dual ligand for A2A and A3 adenosine receptors, as a potential anti-obesity agent. In this study, we compared the anti-obesity effects of LJ-4378 with those of tirzepatide (TZP), a dual agonist of glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide receptors, and one of the most potent FDA-approved obesity therapeutics. Using a mouse model of diet-induced obesity, we assessed the effects of LJ-4378 and TZP on body weight loss, metabolic parameters, and post-treatment weight rebound. Mice fed a high-fat diet (HFD) for 10 weeks were treated with vehicle, LJ-4378, or TZP for 14 days. Both LJ-4378 and TZP significantly reduced body weight, adipose tissue mass, and abdominal fat volume; improved glucose tolerance; reduced white adipose tissue inflammation; and enhanced energy expenditure. To assess the durability of the treatment effects, drug administration was discontinued after 14 days, and the mice remained on the HFD for an additional 4 weeks. Notably, LJ-4378-treated mice exhibited attenuated body weight regain, stable food intake, persistent metabolic benefits, and sustained enhancement of energy metabolism, compared to TZP-treated mice. These findings highlight LJ-4378 as an anti-obesity agent that functions independently of appetite suppression and may offer superior long-term benefits by limiting post-treatment weight rebound and preserving metabolic improvements.
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 mice with diet-induced obesity, tirzepatide reduced body weight versus vehicle.

    In plain wordsIn mice fed a high-fat diet, tirzepatide lowered body weight compared with vehicle.

    Peptide
    Tirzepatide
    Outcome
    DecreaseBody weight
    Study

    mousen: not reported in source

    Diet-induced obesity (high-fat diet)
    Comparator
    Vehicle
    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    Dose not stated · 14 daysAs given in this study (mouse).

    Source sentences

    Summary
    Both LJ-4378 and TZP significantly reduced body weight, adipose tissue mass, and abdominal fat volume; improved glucose tolerance; reduced white adipose tissue inflammation; and enhanced energy expenditure.
    1 context sentence
    Summary · context
    Mice fed a high-fat diet (HFD) for 10 weeks were treated with vehicle, LJ-4378, or TZP for 14 days.
  2. 02AnimalAnimal study (in vivo)Efficacy outcome

    In mice with diet-induced obesity, tirzepatide reduced adipose tissue mass versus vehicle.

    In plain wordsIn mice fed a high-fat diet, tirzepatide lowered fat tissue mass compared with vehicle.

    Peptide
    Tirzepatide
    Outcome
    DecreaseAdipose tissue mass
    Study

    mousen: not reported in source

    Diet-induced obesity (high-fat diet)
    Comparator
    Vehicle
    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    Dose not stated · 14 daysAs given in this study (mouse).

    Source sentences

    Summary
    Both LJ-4378 and TZP significantly reduced body weight, adipose tissue mass, and abdominal fat volume; improved glucose tolerance; reduced white adipose tissue inflammation; and enhanced energy expenditure.
    1 context sentence
    Summary · context
    Mice fed a high-fat diet (HFD) for 10 weeks were treated with vehicle, LJ-4378, or TZP for 14 days.
  3. 03AnimalAnimal study (in vivo)Efficacy outcome

    In mice with diet-induced obesity, tirzepatide reduced abdominal fat volume versus vehicle.

    In plain wordsIn mice fed a high-fat diet, tirzepatide lowered belly fat volume compared with vehicle.

    Peptide
    Tirzepatide
    Outcome
    DecreaseAbdominal fat volume
    Study

    mousen: not reported in source

    Diet-induced obesity (high-fat diet)
    Comparator
    Vehicle
    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    Dose not stated · 14 daysAs given in this study (mouse).

    Source sentences

    Summary
    Both LJ-4378 and TZP significantly reduced body weight, adipose tissue mass, and abdominal fat volume; improved glucose tolerance; reduced white adipose tissue inflammation; and enhanced energy expenditure.
    1 context sentence
    Summary · context
    Mice fed a high-fat diet (HFD) for 10 weeks were treated with vehicle, LJ-4378, or TZP for 14 days.
  4. 04AnimalAnimal study (in vivo)Efficacy outcome

    In mice with diet-induced obesity, tirzepatide improved glucose tolerance versus vehicle.

    In plain wordsIn mice fed a high-fat diet, tirzepatide improved the handling of blood sugar compared with vehicle.

    Peptide
    Tirzepatide
    Outcome
    IncreaseGlucose tolerance
    Study

    mousen: not reported in source

    Diet-induced obesity (high-fat diet)
    Comparator
    Vehicle
    Outcome group
    Glycemic control · Metabolic and weight
    Studied dose
    Dose not stated · 14 daysAs given in this study (mouse).

    Source sentences

    Summary
    Both LJ-4378 and TZP significantly reduced body weight, adipose tissue mass, and abdominal fat volume; improved glucose tolerance; reduced white adipose tissue inflammation; and enhanced energy expenditure.
    1 context sentence
    Summary · context
    Mice fed a high-fat diet (HFD) for 10 weeks were treated with vehicle, LJ-4378, or TZP for 14 days.
  5. 05AnimalAnimal study (in vivo)Efficacy outcome

    In mice with diet-induced obesity, tirzepatide reduced white adipose tissue inflammation versus vehicle.

    In plain wordsIn mice fed a high-fat diet, tirzepatide lowered inflammation in white fat compared with vehicle.

    Peptide
    Tirzepatide
    Outcome
    DecreaseWhite adipose tissue inflammation
    Study

    mousen: not reported in source

    Diet-induced obesity (high-fat diet)
    Comparator
    Vehicle
    Outcome group
    Inflammation markers · Immune and inflammation
    Studied dose
    Dose not stated · 14 daysAs given in this study (mouse).

    Source sentences

    Summary
    Both LJ-4378 and TZP significantly reduced body weight, adipose tissue mass, and abdominal fat volume; improved glucose tolerance; reduced white adipose tissue inflammation; and enhanced energy expenditure.
    1 context sentence
    Summary · context
    Mice fed a high-fat diet (HFD) for 10 weeks were treated with vehicle, LJ-4378, or TZP for 14 days.
  6. 06AnimalAnimal study (in vivo)Efficacy outcome

    In mice with diet-induced obesity, tirzepatide enhanced energy expenditure versus vehicle.

    In plain wordsIn mice fed a high-fat diet, tirzepatide raised energy use compared with vehicle.

    Peptide
    Tirzepatide
    Outcome
    IncreaseEnergy expenditure
    Study

    mousen: not reported in source

    Diet-induced obesity (high-fat diet)
    Comparator
    Vehicle
    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    Dose not stated · 14 daysAs given in this study (mouse).

    Source sentences

    Summary
    Both LJ-4378 and TZP significantly reduced body weight, adipose tissue mass, and abdominal fat volume; improved glucose tolerance; reduced white adipose tissue inflammation; and enhanced energy expenditure.
    1 context sentence
    Summary · context
    Mice fed a high-fat diet (HFD) for 10 weeks were treated with vehicle, LJ-4378, or TZP for 14 days.
  7. 07AnimalAnimal study (in vivo)Efficacy outcome

    In mice with diet-induced obesity, body weight regain after stopping tirzepatide was greater than after LJ-4378.

    In plain wordsIn mice, weight came back more after tirzepatide was stopped than after LJ-4378 was stopped.

    Peptide
    Tirzepatide
    Outcome
    IncreaseBody weight regain after stopping treatment
    Study

    mousen: not reported in source

    Diet-induced obesity (high-fat diet)
    Comparator
    LJ-4378
    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    Dose not stated · 14 daysAs given in this study (mouse).

    Source sentences

    Summary
    Notably, LJ-4378-treated mice exhibited attenuated body weight regain, stable food intake, persistent metabolic benefits, and sustained enhancement of energy metabolism, compared to TZP-treated mice.
    1 context sentence
    Summary · context
    Mice fed a high-fat diet (HFD) for 10 weeks were treated with vehicle, LJ-4378, or TZP for 14 days.
  8. 08AnimalAnimal study (in vivo)Efficacy outcome

    In mice with diet-induced obesity, metabolic benefits and the enhancement of energy metabolism persisted less after stopping tirzepatide than after LJ-4378.

    In plain wordsIn mice, benefits to metabolism lasted less long after tirzepatide was stopped than after LJ-4378 was stopped.

    Peptide
    Tirzepatide
    Outcome
    DecreasePersistence of metabolic benefits and energy metabolism after stopping treatment
    Study

    mousen: not reported in source

    Diet-induced obesity (high-fat diet)
    Comparator
    LJ-4378
    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    Dose not stated · 14 daysAs given in this study (mouse).

    Source sentences

    Summary
    Notably, LJ-4378-treated mice exhibited attenuated body weight regain, stable food intake, persistent metabolic benefits, and sustained enhancement of energy metabolism, compared to TZP-treated mice.
    1 context sentence
    Summary · context
    Mice fed a high-fat diet (HFD) for 10 weeks were treated with vehicle, LJ-4378, or TZP for 14 days.

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

    12 Oct 2026, 12:58 UTC

    Study results updated

  2. Version 1

    9 Oct 2026, 03:07 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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