Melanocortin 4 receptors in the paraventricular nucleus modulate the adipose afferent reflex in rat.

Li P, Sun HJ, Zhang LL, Ding L, Han Y, Zhu GQ, Zhou YB

PloS one11 Nov 2013Cited by 15 (Europe PMC)

PMID24244673PMCIDPMC3823614DOI10.1371/journal.pone.0080295PepBankPUB-24244673

Summary

Background and aimParaventricular nucleus (PVN) of hypothalamus is an important central component in modulating adipose afferent reflex (AAR). Melanocortin receptors (MC3/4Rs) expressions are found in the hypothalamic PVN. This study was designed to determine the roles of MC3/4Rs in the PVN in modulating the AAR and its downstream signaling pathway in normal rats.Methodology/principal findingsRenal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) were recorded in anaesthetized rats. AAR was evaluated using RSNA and MAP responses to capsaicin injection into the inguinal white adipose tissue (iWAT). Microinjection of the MC3/4R agonist melanotan II (MTII) into the PVN enhanced the AAR. The MC3/4R antagonist SHU9119 or MC4R antagonist HS024 attenuated the AAR and abolished MTII-induced AAR response. The adenylate cyclase (AC) inhibitor SQ22536 or the protein kinase A (PKA) inhibitor Rp-cAMP attenuated the AAR and the effect of MTII on the AAR was abolished by pretreatment with SQ22536 or Rp-cAMP in the PVN. Furthermore, both PVN microinjection of MTII and iWAT injection of capsaicin increased the cAMP level in the PVN. SHU9119 in the PVN abolished the increase in cAMP level which induced by iWAT injection of capsaicin.ConclusionThe activation of MC4Rs rather than MC3Rs enhances the AAR, and a cAMP-PKA pathway is involved in the effects of MC4Rs in the PVN.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study4

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

01AnimalAnimal study (in vivo)Mechanism
In anaesthetized rats, microinjection of melanotan II into the paraventricular nucleus enhanced the adipose afferent reflex.
In plain wordsIn rats, melanotan II injected into a brain region called the PVN made a fat-to-nerve reflex stronger.
Peptide
Melanotan II
Outcome
IncreaseAdipose afferent reflex (AAR) after MTII
Study
ratn: not reported in source
Outcome group
Receptor activity and mechanism · Nervous system and cognition
Studied dose
Dose not stated · microinjection into the paraventricular nucleusAs given in this study (rat).
Source sentences
Summary
Microinjection of the MC3/4R agonist melanotan II (MTII) into the PVN enhanced the AAR.
1 context sentence(design, population, supporting numbers)
Summary · context
Renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) were recorded in anaesthetized rats.
Show in the study text Report a problemFND-2424467301
02AnimalAnimal study (in vivo)Mechanism
In rats, PVN microinjection of MTII increased the cAMP level in the PVN.
In plain wordsIn rats, melanotan II injected into the PVN raised the level of the signal molecule cAMP there.
Peptide
Melanotan II
Outcome
IncreasecAMP level in the PVN after MTII
Study
ratn: not reported in source
Outcome group
Receptor activity and mechanism · Nervous system and cognition
Studied dose
Dose not stated · microinjection into the paraventricular nucleusAs given in this study (rat).
Source sentences
Summary
both PVN microinjection of MTII and iWAT injection of capsaicin increased the cAMP level in the PVN.
1 context sentence(design, population, supporting numbers)
Summary · context
Renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) were recorded in anaesthetized rats.
Show in the study text Report a problemFND-2424467304

Studies that did not test the peptide alone2

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.

03AnimalNot a test of Melanotan II aloneAnimal study (in vivo)Mechanism
In anaesthetized rats, the MC3/4R antagonist SHU9119 and the MC4R antagonist HS024 abolished the MTII-induced AAR response.
In plain wordsIn rats, drugs that block melanocortin receptors removed the stronger reflex that melanotan II caused.
Peptide
Melanotan II
Outcome
DecreaseMTII-induced AAR response with MC3/4R or MC4R antagonist
Study
ratn: not reported in source
Outcome group
Receptor activity and mechanism · Nervous system and cognition
Source sentences
Summary
The MC3/4R antagonist SHU9119 or MC4R antagonist HS024 attenuated the AAR and abolished MTII-induced AAR response.
1 context sentence(design, population, supporting numbers)
Summary · context
Renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) were recorded in anaesthetized rats.
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.
Show in the study text Report a problemFND-2424467302
04AnimalNot a test of Melanotan II aloneAnimal study (in vivo)Mechanism
In anaesthetized rats, pretreatment with the adenylate cyclase inhibitor SQ22536 or the PKA inhibitor Rp-cAMP in the PVN abolished the effect of MTII on the AAR.
In plain wordsIn rats, blocking the cAMP-PKA pathway in the PVN removed the effect of melanotan II on the reflex.
Peptide
Melanotan II
Outcome
DecreaseMTII-induced AAR response with AC or PKA inhibitor
Study
ratn: not reported in source
Outcome group
Receptor activity and mechanism · Nervous system and cognition
Source sentences
Summary
the effect of MTII on the AAR was abolished by pretreatment with SQ22536 or Rp-cAMP in the PVN.
1 context sentence(design, population, supporting numbers)
Summary · context
Renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) were recorded in anaesthetized rats.
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.
Show in the study text Report a problemFND-2424467303

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

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Version 2Current
10 Oct 2026, 09:43 UTC
Study results updated
Version 1
9 Oct 2026, 03:04 UTC
First added · source update from Europe PMC

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