Altered energy balance causes selective changes in melanocortin-4(MC4-R), but not melanocortin-3 (MC3-R), receptors in specific hypothalamic regions: further evidence that activation of MC4-R is a physiological inhibitor of feeding.

Harrold JA, Widdowson PS, Williams G

Diabetes1 Feb 1999Cited by 104 (Europe PMC)

PMID10334300DOI10.2337/diabetes.48.2.267PepBankPUB-10334300

Publisher page PubMedAsk about this study

Summary

The text of this summary is not shown here, because the article license does not allow reuse. Read it at the source (opens in a new tab)

Text rights: Publisher copyright. Results still quote short attributed sentences.

Results from this study4

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

Studies that did not test the peptide alone4

In this study, Melanotan I (afamelanotide) 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 I (afamelanotide).

01AnimalNot a test of Melanotan I (afamelanotide) aloneAnimal study (in vivo)Mechanism
In rats after 10 days of food restriction with 14% weight loss, hypothalamic MC4-R density increased by 20-65% in the VMH, ARC, ME and DMH.
In plain wordsIn underfed rats, melanocortin 4 receptors rose in several brain areas that control feeding.
Peptide
Melanotan I (afamelanotide)
Outcome
IncreaseMC4-R density after food restriction
Study
ratn: not reported in source
Outcome group
Receptor activity and mechanism · Nervous system and cognition
Measurements
MC4-R density increase
20 to 65%
VMH, ARC, ME and DMH after food restriction
Source sentences
Summary
After 10-days of food restriction (14% weight loss), density of MC4-R was significantly increased by 20-65% in the VMH, ARC, ME, and DMH, with no changes elsewhere.
1 context sentence(design, population, supporting numbers)
Summary · context
MC3-R and MC4-R were measured by quantitative autoradiography in brain sections using 125I-labeled Nle4-D-Phe7-alpha-MSH (125I-NDP-MSH) and discriminated by masking MC3-R with excess unlabelled gamma2-MSH.
In this study, Melanotan I (afamelanotide) 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 I (afamelanotide).
Report a problemFND-1033430001
02AnimalNot a test of Melanotan I (afamelanotide) aloneAnimal study (in vivo)Mechanism
In obese (fa/fa) Zucker rats, MC4-R density increased by 43-98% in the same hypothalamic regions.
In plain wordsIn obese Zucker rats, melanocortin 4 receptors rose in the same brain areas.
Peptide
Melanotan I (afamelanotide)
Outcome
IncreaseMC4-R density in obese Zucker rats
Study
ratn: not reported in source
Outcome group
Receptor activity and mechanism · Nervous system and cognition
Measurements
MC4-R density increase
43 to 98%
obese Zucker rats
Source sentences
Summary
Similarly, obese (fa/fa) Zucker rats showed 43-98% increases in MC4-R in the same regions.
1 context sentence(design, population, supporting numbers)
Summary · context
MC3-R and MC4-R were measured by quantitative autoradiography in brain sections using 125I-labeled Nle4-D-Phe7-alpha-MSH (125I-NDP-MSH) and discriminated by masking MC3-R with excess unlabelled gamma2-MSH.
In this study, Melanotan I (afamelanotide) 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 I (afamelanotide).
Report a problemFND-1033430002
03AnimalNot a test of Melanotan I (afamelanotide) aloneAnimal study (in vivo)Mechanism
In rats with diet-induced obesity (18% heavier than controls), MC4-R binding was significantly decreased, especially in the VMH, ARC and ME.
In plain wordsIn rats made obese by diet, melanocortin 4 receptors fell in brain areas that control feeding.
Peptide
Melanotan I (afamelanotide)
Outcome
DecreaseMC4-R binding in diet-induced obesity
Study
ratn: not reported in source
Outcome group
Receptor activity and mechanism · Nervous system and cognition
Source sentences
Summary
By contrast, rats with diet-induced obesity (18% heavier than controls) showed significantly decreased binding to MC4-R, especially in the VMH, ARC, and ME.
1 context sentence(design, population, supporting numbers)
Summary · context
MC3-R and MC4-R were measured by quantitative autoradiography in brain sections using 125I-labeled Nle4-D-Phe7-alpha-MSH (125I-NDP-MSH) and discriminated by masking MC3-R with excess unlabelled gamma2-MSH.
In this study, Melanotan I (afamelanotide) 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 I (afamelanotide).
Report a problemFND-1033430003
04AnimalNot a test of Melanotan I (afamelanotide) aloneAnimal study (in vivo)Mechanism
In the food-restricted and obese rat models, MC3-R showed no significant alterations.
In plain wordsIn rats, melanocortin 3 receptors did not change in any of the models.
Peptide
Melanotan I (afamelanotide)
Outcome
No significant changeMC3-R density across models
Study
ratn: not reported in source
Outcome group
Receptor activity and mechanism · Nervous system and cognition
Source sentences
Summary
MC3-R showed no significant alterations in any model.
1 context sentence(design, population, supporting numbers)
Summary · context
MC3-R and MC4-R were measured by quantitative autoradiography in brain sections using 125I-labeled Nle4-D-Phe7-alpha-MSH (125I-NDP-MSH) and discriminated by masking MC3-R with excess unlabelled gamma2-MSH.
In this study, Melanotan I (afamelanotide) 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 I (afamelanotide).
Report a problemFND-1033430004

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.

Version 2Current
13 Oct 2026, 21:44 UTC
Study results updated
Version 1
13 Oct 2026, 16:31 UTC
First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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MeSH terms

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