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Study · Not a test of the peptide alone · 2025

6 results

Loss of melanocortin receptor accessory protein 2 in melanocortin-4 receptor neurons protect from obesity-associated autonomic and cardiovascular dysfunctions.

Guo DF, Williams PA, Olson A, Morgan DA, Herz H, Resch J, Atasoy D, Stauss HM, Sebag JA, Rahmouni K

Cardiovascular research1 Oct 2025Cited by 8 (Europe PMC)

PMID40244925 (opens in a new tab)PMCIDPMC12551390 (opens in a new tab)DOI10.1093/cvr/cvaf067 (opens in a new tab)PepBankPUB-40244925
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Summary

AimsThe melanocortin receptor accessory protein 2 (MRAP2), which is abundantly expressed in the brain including the hypothalamus, has emerged as a key regulator of melanocortin-4 receptor (MC4R) activity. We sought to delineate the physiological significance of MRAP2 in MC4R neurons, with a particular focus on metabolic, autonomic and cardiovascular functions.Methods and resultsSelective deletion of MRAP2 in MC4R neurons causes obesity that was associated with hyperphagia and impairment in glucose homeostasis and insulin sensitivity. MC4R agonist Melatonan II (MTII)-induced anorectic effects were blunted in mice lacking MRAP2 in MC4R neurons, whereas Celastrol retained its efficacy in reducing food intake and body weight. MRAP2 deletion also reduced baseline sympathetic nerve activity (SNA), particularly the SNA subserving the kidney. This was associated with reduced innervation of the kidney. In addition, MTII-induced increases in renal and brown adipose tissue (BAT) SNA as well as hepatic vagal nerve activity were significantly attenuated in MC4R neuron MRAP2-deficient mice. Transynaptic tracing revealed that MC4R neurons projecting to BAT and kidneys were localized to specific brain nuclei including the paraventricular nucleus of the hypothalamus, providing anatomical substrate for MRAP2 regulation of sympathetic outflow. Although the loss of MRAP2 in MC4R neurons did not affect arterial pressure, it caused a significant decrease in heart rate and baroreflex sensitivity. Finally, MRAP2 deficiency in MC4R neurons attenuated MTII-induced increase in arterial pressure and heart rate.ConclusionThese findings demonstrate that in addition to its role in energy balance and glucose homeostasis MRAP2 in MC4R neurons is crucial for cardiovascular autonomic regulation and is required for the development of obesity-associated hypertension and autonomic dysfunction.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study6

No result from this study comes from a test of the peptide.

Studies that did not test the peptide alone6

In this study, Melanotan II 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 Melanotan II.

  1. 01AnimalNot a test of Melanotan II aloneAnimal study (in vivo)Mechanism

    In mice lacking MRAP2 in MC4R neurons, the anorectic effect of the MC4R agonist MTII was blunted.

    In plain wordsIn mice lacking MRAP2 in these neurons, the appetite-reducing effect of MTII was weaker.

    Peptide
    Melanotan II
    Outcome
    DecreaseMTII anorectic effect in MRAP2-deficient mice
    Study

    mousen: not reported in source

    mice lacking MRAP2 in MC4R neurons
    Outcome group
    Appetite and food intake · Metabolic and weight

    Source sentences

    Summary
    MC4R agonist Melatonan II (MTII)-induced anorectic effects were blunted in mice lacking MRAP2 in MC4R neurons
    1 context sentence
    Summary · context
    We sought to delineate the physiological significance of MRAP2 in MC4R neurons, with a particular focus on metabolic, autonomic and cardiovascular functions.

    In this study, Melanotan II 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 Melanotan II.

  2. 02AnimalNot a test of Melanotan II aloneAnimal study (in vivo)Mechanism

    In mice lacking MRAP2 in MC4R neurons, the MTII-induced increase in renal sympathetic nerve activity was significantly attenuated.

    In plain wordsIn mice lacking MRAP2 in these neurons, MTII raised kidney nerve activity less.

    Peptide
    Melanotan II
    Outcome
    DecreaseMTII-induced renal sympathetic nerve activity in MRAP2-deficient mice
    Study

    mousen: not reported in source

    mice lacking MRAP2 in MC4R neurons
    Outcome group
    Brain and neuronal activity · Cardiovascular

    Source sentences

    Summary
    In addition, MTII-induced increases in renal and brown adipose tissue (BAT) SNA as well as hepatic vagal nerve activity were significantly attenuated in MC4R neuron MRAP2-deficient mice.
    1 context sentence
    Summary · context
    We sought to delineate the physiological significance of MRAP2 in MC4R neurons, with a particular focus on metabolic, autonomic and cardiovascular functions.

    In this study, Melanotan II 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 Melanotan II.

  3. 03AnimalNot a test of Melanotan II aloneAnimal study (in vivo)Mechanism

    In mice lacking MRAP2 in MC4R neurons, the MTII-induced increase in brown adipose tissue sympathetic nerve activity was significantly attenuated.

    In plain wordsIn mice lacking MRAP2 in these neurons, MTII raised brown fat nerve activity less.

    Peptide
    Melanotan II
    Outcome
    DecreaseMTII-induced brown adipose tissue sympathetic nerve activity in MRAP2-deficient mice
    Study

    mousen: not reported in source

    mice lacking MRAP2 in MC4R neurons
    Outcome group
    Brain and neuronal activity · Cardiovascular

    Source sentences

    Summary
    In addition, MTII-induced increases in renal and brown adipose tissue (BAT) SNA as well as hepatic vagal nerve activity were significantly attenuated in MC4R neuron MRAP2-deficient mice.
    1 context sentence
    Summary · context
    We sought to delineate the physiological significance of MRAP2 in MC4R neurons, with a particular focus on metabolic, autonomic and cardiovascular functions.

    In this study, Melanotan II 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 Melanotan II.

  4. 04AnimalNot a test of Melanotan II aloneAnimal study (in vivo)Mechanism

    In mice lacking MRAP2 in MC4R neurons, the MTII-induced increase in hepatic vagal nerve activity was significantly attenuated.

    In plain wordsIn mice lacking MRAP2 in these neurons, MTII raised liver vagus nerve activity less.

    Peptide
    Melanotan II
    Outcome
    DecreaseMTII-induced hepatic vagal nerve activity in MRAP2-deficient mice
    Study

    mousen: not reported in source

    mice lacking MRAP2 in MC4R neurons
    Outcome group
    Brain and neuronal activity · Cardiovascular

    Source sentences

    Summary
    In addition, MTII-induced increases in renal and brown adipose tissue (BAT) SNA as well as hepatic vagal nerve activity were significantly attenuated in MC4R neuron MRAP2-deficient mice.
    1 context sentence
    Summary · context
    We sought to delineate the physiological significance of MRAP2 in MC4R neurons, with a particular focus on metabolic, autonomic and cardiovascular functions.

    In this study, Melanotan II 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 Melanotan II.

  5. 05AnimalNot a test of Melanotan II aloneAnimal study (in vivo)Mechanism

    In mice lacking MRAP2 in MC4R neurons, the MTII-induced increase in arterial pressure was attenuated.

    In plain wordsIn mice lacking MRAP2 in these neurons, MTII raised blood pressure less.

    Peptide
    Melanotan II
    Outcome
    DecreaseMTII-induced arterial pressure rise in MRAP2-deficient mice
    Study

    mousen: not reported in source

    mice lacking MRAP2 in MC4R neurons
    Outcome group
    Blood pressure · Cardiovascular

    Source sentences

    Summary
    Finally, MRAP2 deficiency in MC4R neurons attenuated MTII-induced increase in arterial pressure and heart rate.
    1 context sentence
    Summary · context
    We sought to delineate the physiological significance of MRAP2 in MC4R neurons, with a particular focus on metabolic, autonomic and cardiovascular functions.

    In this study, Melanotan II 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 Melanotan II.

  6. 06AnimalNot a test of Melanotan II aloneAnimal study (in vivo)Mechanism

    In mice lacking MRAP2 in MC4R neurons, the MTII-induced increase in heart rate was attenuated.

    In plain wordsIn mice lacking MRAP2 in these neurons, MTII raised heart rate less.

    Peptide
    Melanotan II
    Outcome
    DecreaseMTII-induced heart rate rise in MRAP2-deficient mice
    Study

    mousen: not reported in source

    mice lacking MRAP2 in MC4R neurons
    Outcome group
    Heart function · Cardiovascular

    Source sentences

    Summary
    Finally, MRAP2 deficiency in MC4R neurons attenuated MTII-induced increase in arterial pressure and heart rate.
    1 context sentence
    Summary · context
    We sought to delineate the physiological significance of MRAP2 in MC4R neurons, with a particular focus on metabolic, autonomic and cardiovascular functions.

    In this study, Melanotan II 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 Melanotan II.

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

    10 Oct 2026, 09:43 UTC

    Study results updated

  2. Version 1

    9 Oct 2026, 03:04 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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