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

7 results

The MC4R agonist, setmelanotide, is associated with an improvement in hypercapnic chemosensitivity and weight loss in male mice.

Rivera A, Framnes-DeBoer SN, Arble DM

Respiratory physiology & neurobiology13 Nov 2024Cited by 3 (Europe PMC)

PMID39542230 (opens in a new tab)PMCIDPMC12323632 (opens in a new tab)DOI10.1016/j.resp.2024.104370 (opens in a new tab)PepBankPUB-39542230
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Summary

Obesity increases the risk of respiratory diseases that reduce respiratory chemosensitivity, such as Obesity Hypoventilation Syndrome and sleep apnea. Recent evidence suggests that obesity-related changes in the brain, including alterations in melanocortin signaling via the melanocortin-4 receptor (MC4R), may underly altered chemosensitivity. Setmelanotide, an MC4R agonist, causes weight loss in both humans and animal models. However, it is unknown the extent to which setmelanotide affects respiratory chemosensitivity independent of body weight loss. The present study uses diet-induced obese, male C57bl/6 J mice to determine the extent to which acute setmelanotide treatment affects the hypercapnic ventilatory response (HCVR). We find that ten days of daily setmelanotide treatment at 1 mg/kg, but not 0.2 mg/kg, is sufficient to cause weight loss and increase HCVR. In a separate group of animals, we find that we can emulate setmelanotide's effect on weight loss by restricting daily calories to match the hypophagia triggered by setmelanotide. These pair-fed animals exhibit improvements in HCVR similar to those who receive setmelanotide. We conclude that acute treatment with setmelanotide is as effective as weight loss at improving respiratory hypercapnic chemosensitivity.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study7

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

  1. 01AnimalAnimal study (in vivo)Efficacy outcome

    In obese male mice, ten days of daily setmelanotide at 1 mg/kg caused weight loss.

    In plain wordsIn obese male mice, daily setmelanotide at 1 mg/kg caused weight loss over ten days.

    Peptide
    Setmelanotide
    Outcome
    DecreaseWeight loss at higher dose
    Study

    mousen: not reported in source

    Diet-induced obese male C57bl/6 J mice
    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    1 mg/kg daily · Ten daysAs given in this study (mouse).

    Source sentences

    Summary
    We find that ten days of daily setmelanotide treatment at 1 mg/kg, but not 0.2 mg/kg, is sufficient to cause weight loss and increase HCVR.
    1 context sentence
    Summary · context
    The present study uses diet-induced obese, male C57bl/6 J mice to determine the extent to which acute setmelanotide treatment affects the hypercapnic ventilatory response (HCVR).
  2. 02AnimalAnimal study (in vivo)Efficacy outcome

    In obese male mice, ten days of daily setmelanotide at 0.2 mg/kg did not cause weight loss.

    In plain wordsIn obese male mice, daily setmelanotide at 0.2 mg/kg did not cause weight loss over ten days.

    Peptide
    Setmelanotide
    Outcome
    No significant changeWeight loss at lower dose
    Study

    mousen: not reported in source

    Diet-induced obese male C57bl/6 J mice
    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    0.2 mg/kg daily · Ten daysAs given in this study (mouse).

    Source sentences

    Summary
    We find that ten days of daily setmelanotide treatment at 1 mg/kg, but not 0.2 mg/kg, is sufficient to cause weight loss and increase HCVR.
    1 context sentence
    Summary · context
    The present study uses diet-induced obese, male C57bl/6 J mice to determine the extent to which acute setmelanotide treatment affects the hypercapnic ventilatory response (HCVR).
  3. 03AnimalAnimal study (in vivo)Efficacy outcome

    In obese male mice, ten days of daily setmelanotide at 1 mg/kg increased the hypercapnic ventilatory response.

    In plain wordsIn obese male mice, daily setmelanotide at 1 mg/kg increased the breathing response to carbon dioxide over ten days.

    Peptide
    Setmelanotide
    Outcome
    IncreaseHypercapnic ventilatory response at higher dose
    Study

    mousen: not reported in source

    Diet-induced obese male C57bl/6 J mice
    Outcome group
    Respiratory function · Respiratory
    Studied dose
    1 mg/kg daily · Ten daysAs given in this study (mouse).

    Source sentences

    Summary
    We find that ten days of daily setmelanotide treatment at 1 mg/kg, but not 0.2 mg/kg, is sufficient to cause weight loss and increase HCVR.
    1 context sentence
    Summary · context
    The present study uses diet-induced obese, male C57bl/6 J mice to determine the extent to which acute setmelanotide treatment affects the hypercapnic ventilatory response (HCVR).
  4. 04AnimalAnimal study (in vivo)Efficacy outcome

    In obese male mice, ten days of daily setmelanotide at 0.2 mg/kg did not increase the hypercapnic ventilatory response.

    In plain wordsIn obese male mice, daily setmelanotide at 0.2 mg/kg did not increase the breathing response to carbon dioxide over ten days.

    Peptide
    Setmelanotide
    Outcome
    No significant changeHypercapnic ventilatory response at lower dose
    Study

    mousen: not reported in source

    Diet-induced obese male C57bl/6 J mice
    Outcome group
    Respiratory function · Respiratory
    Studied dose
    0.2 mg/kg daily · Ten daysAs given in this study (mouse).

    Source sentences

    Summary
    We find that ten days of daily setmelanotide treatment at 1 mg/kg, but not 0.2 mg/kg, is sufficient to cause weight loss and increase HCVR.
    1 context sentence
    Summary · context
    The present study uses diet-induced obese, male C57bl/6 J mice to determine the extent to which acute setmelanotide treatment affects the hypercapnic ventilatory response (HCVR).
  5. 05AnimalAnimal study (in vivo)Efficacy outcome

    In obese male mice, setmelanotide triggered hypophagia used to set the calorie restriction in pair-fed animals.

    In plain wordsIn obese male mice, setmelanotide reduced food intake.

    Peptide
    Setmelanotide
    Outcome
    DecreaseHypophagia
    Study

    mousen: not reported in source

    Diet-induced obese male C57bl/6 J mice
    Outcome group
    Appetite and food intake · Metabolic and weight
    Studied dose
    Dose not stated

    Source sentences

    Summary
    In a separate group of animals, we find that we can emulate setmelanotide's effect on weight loss by restricting daily calories to match the hypophagia triggered by setmelanotide.
    1 context sentence
    Summary · context
    The present study uses diet-induced obese, male C57bl/6 J mice to determine the extent to which acute setmelanotide treatment affects the hypercapnic ventilatory response (HCVR).
  6. 06AnimalAnimal study (in vivo)Efficacy outcome

    In obese male mice, calorie restriction emulated the weight loss produced by setmelanotide.

    In plain wordsIn obese male mice, calorie restriction matched weight loss with setmelanotide.

    Peptide
    Setmelanotide
    Outcome
    No significant changeWeight loss versus pair feeding
    Study

    mousen: not reported in source

    Diet-induced obese male C57bl/6 J mice
    Comparator
    Calorie-restricted pair-fed mice
    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    Dose not stated

    Source sentences

    Summary
    In a separate group of animals, we find that we can emulate setmelanotide's effect on weight loss by restricting daily calories to match the hypophagia triggered by setmelanotide.
    1 context sentence
    Summary · context
    The present study uses diet-induced obese, male C57bl/6 J mice to determine the extent to which acute setmelanotide treatment affects the hypercapnic ventilatory response (HCVR).
  7. 07AnimalAnimal study (in vivo)Efficacy outcome

    In obese male mice, setmelanotide and pair feeding produced similar improvements in hypercapnic ventilatory response.

    In plain wordsIn obese male mice, setmelanotide and pair feeding produced similar improvements in the breathing response to carbon dioxide.

    Peptide
    Setmelanotide
    Outcome
    No significant changeHypercapnic ventilatory response versus pair feeding
    Study

    mousen: not reported in source

    Diet-induced obese male C57bl/6 J mice
    Comparator
    Calorie-restricted pair-fed mice
    Outcome group
    Respiratory function · Respiratory
    Studied dose
    Dose not stated

    Source sentences

    Summary
    These pair-fed animals exhibit improvements in HCVR similar to those who receive setmelanotide.
    2 context sentences
    Summary · context
    In a separate group of animals, we find that we can emulate setmelanotide's effect on weight loss by restricting daily calories to match the hypophagia triggered by setmelanotide.
    Summary · context
    The present study uses diet-induced obese, male C57bl/6 J mice to determine the extent to which acute setmelanotide treatment affects the hypercapnic ventilatory response (HCVR).

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

    28 Oct 2026, 02:03 UTC

    Study results updated

  2. Version 1

    27 Oct 2026, 16:36 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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