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

3 results

Targeting melanocortin 4 receptor to treat sleep-disordered breathing in mice.

Amorim MR, Williams NR, Aung O, Ruiz MA, Anokye-Danso F, de Deus JL, Xiong J, Dergacheva O, Bevans-Fonti S, Lee SM, Berger JS, Wu MN, Ahima RS, Mendelowitz D, Polotsky VY

The Journal of clinical investigation15 Apr 2025Cited by 6 (Europe PMC)

PMID40232848 (opens in a new tab)PMCIDPMC12165796 (opens in a new tab)DOI10.1172/jci177823 (opens in a new tab)PepBankPUB-40232848
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Summary

Weight loss medications are emerging candidates for pharmacotherapy of sleep-disordered breathing (SDB). A melanocortin 4 receptor (MC4R) agonist, setmelanotide (Set), is used to treat obesity caused by abnormal melanocortin and leptin signaling. We hypothesized that Set can treat SDB in mice with diet-induced obesity. We performed a proof-of-concept randomized crossover trial of a single dose of Set versus vehicle and a 2-week daily Set versus vehicle trial, examined colocalization of Mc4r mRNAs with the markers of CO2-sensing neurons Phox2b and neuromedin B in the brainstem, and expressed Cre-dependent designer receptors exclusively activated by designer drugs (DREADDs) or caspase in obese Mc4r-Cre mice. Set increased minute ventilation across sleep/wake states, enhanced the hypercapnic ventilatory response (HCVR), and abolished apneas during sleep. Phox2b+ neurons in the nucleus of the solitary tract (NTS) and the parafacial region expressed Mc4r. Chemogenetic stimulation of the MC4R+ neurons in the parafacial region, but not in the NTS, augmented HCVR without any changes in metabolism. Caspase elimination of the parafacial MC4R+ neurons abolished effects of Set on HCVR. Parafacial MC4R+ neurons projected to the respiratory premotor neurons retrogradely labeled from C3-C4. In conclusion, MC4R agonists enhance the HCVR and treat SDB by acting on the parafacial MC4R+ neurons.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study3

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

  1. 01AnimalAnimal study (in vivo)Efficacy outcome

    In obese mice, setmelanotide increased minute ventilation across sleep and wake states versus vehicle.

    In plain wordsIn mice with obesity, setmelanotide increased breathing volume versus vehicle.

    Peptide
    Setmelanotide
    Outcome
    IncreaseMinute ventilation
    Study

    mousen: not reported in source

    Diet-induced obesity
    Comparator
    Vehicle
    Outcome group
    Respiratory function · Respiratory
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Set increased minute ventilation across sleep/wake states, enhanced the hypercapnic ventilatory response (HCVR), and abolished apneas during sleep.
  2. 02AnimalAnimal study (in vivo)Efficacy outcome

    In obese mice, setmelanotide enhanced the hypercapnic ventilatory response versus vehicle.

    In plain wordsIn mice with obesity, setmelanotide increased the breathing response to carbon dioxide versus vehicle.

    Peptide
    Setmelanotide
    Outcome
    IncreaseHypercapnic ventilatory response
    Study

    mousen: not reported in source

    Diet-induced obesity
    Comparator
    Vehicle
    Outcome group
    Respiratory function · Respiratory
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Set increased minute ventilation across sleep/wake states, enhanced the hypercapnic ventilatory response (HCVR), and abolished apneas during sleep.
  3. 03AnimalAnimal study (in vivo)Efficacy outcome

    In obese mice, setmelanotide abolished sleep apneas versus vehicle.

    In plain wordsIn mice with obesity, setmelanotide eliminated sleep breathing pauses versus vehicle.

    Peptide
    Setmelanotide
    Outcome
    DecreaseSleep apneas
    Study

    mousen: not reported in source

    Diet-induced obesity
    Comparator
    Vehicle
    Outcome group
    Sleep · Respiratory
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Set increased minute ventilation across sleep/wake states, enhanced the hypercapnic ventilatory response (HCVR), and abolished apneas during sleep.

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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