Evidence map›Paper›PMID 39914386›Full record

ArticleCell reports. Medicine2025

The metabolic and cardiovascular effects of amphetamine are partially mediated by the central melanocortin system.

Stephanie E Simonds, Jack T Pryor, Brian Y H Lam, Georgina K Dowsett, Tomris Mustafa, Astrid Munder, Kayla Elysee, Eglantine Balland, Lachlan O Cowley, Giles S H Yeo and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports. Medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Stephanie E SimondsDepartment of Physiology, Metabolism, Diabetes, and Obesity Programme, Monash Biomedicine Discovery Institute Monash University, Clayton, VIC, Australia. Electronic address: stephanie.simonds@monash.edu.
Jack T PryorDepartment of Physiology, Metabolism, Diabetes, and Obesity Programme, Monash Biomedicine Discovery Institute Monash University, Clayton, VIC, Australia.
Brian Y H LamMRC Metabolic Diseases Unit, University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK.
Georgina K DowsettMRC Metabolic Diseases Unit, University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK.
Tomris MustafaDepartment of Physiology, Metabolism, Diabetes, and Obesity Programme, Monash Biomedicine Discovery Institute Monash University, Clayton, VIC, Australia.
Astrid MunderDepartment of Physiology, Metabolism, Diabetes, and Obesity Programme, Monash Biomedicine Discovery Institute Monash University, Clayton, VIC, Australia.
Kayla ElyseeDepartment of Physiology, Metabolism, Diabetes, and Obesity Programme, Monash Biomedicine Discovery Institute Monash University, Clayton, VIC, Australia.
Eglantine BallandDepartment of Physiology, Metabolism, Diabetes, and Obesity Programme, Monash Biomedicine Discovery Institute Monash University, Clayton, VIC, Australia.
Lachlan O CowleyDepartment of Physiology, Metabolism, Diabetes, and Obesity Programme, Monash Biomedicine Discovery Institute Monash University, Clayton, VIC, Australia.
Giles S H YeoMRC Metabolic Diseases Unit, University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK.
Andrew LawrenceMental Health Theme, The Florey Institute of Neuroscience and Mental Health, Parkville, VIC 3052, Australia; Florey Department of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC 3052, Australia.
David C SpanswickDepartment of Physiology, Metabolism, Diabetes, and Obesity Programme, Monash Biomedicine Discovery Institute Monash University, Clayton, VIC, Australia; Warwick Medical School, Division of Biomedical Sciences, University of Warwick, CV4 7AL Coventry, UK.
Michael A CowleyDepartment of Physiology, Metabolism, Diabetes, and Obesity Programme, Monash Biomedicine Discovery Institute Monash University, Clayton, VIC, Australia. Electronic address: michael.cowley@monash.edu.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Amphetamine (AMPH) exerts metabolic and cardiovascular effects. The central melanocortin system is a key regulator of both metabolic and cardiovascular functions. Here, we show that the melanocortin system partially mediates AMPH-induced anorexia, energy expenditure, tachycardia, and hypertension. AMPH increased α-melanocyte stimulating hormone (αMSH) secretion from the hypothalamus, elevated blood pressure and heart rate (HR), increased brown adipose tissue (BAT) thermogenesis, and reduced both food intake (FI) and body weight (BW). In melanocortin 4 receptor-deficient (MC4R knockout [KO]) mice, metabolic and cardiovascular effects of AMPH were significantly attenuated. Antagonism of serotonergic and noradrenergic neurotransmitter systems attenuated AMPH-induced αMSH secretion as well as AMPH-induced metabolic and cardiovascular effects. We propose that AMPH increases serotonergic activation of proopiomelanocortin (POMC) neurons and reduces the noradrenergic inhibition of POMC neurons, thereby disinhibiting them. Together, these presynaptic mechanisms result in increased POMC activity, increased αMSH secretion, and increased activation of MC4R pathways that regulate both the metabolic and cardiovascular systems.

Indexed as

AmphetamineCardiovascular SystemMelanocortinsAdipose Tissue, Brownalpha-MSHAnimalsBlood PressureBody WeightEatingEnergy MetabolismHeart RateHypothalamusMaleMiceMice, Inbred C57BLMice, Knockoutalpha-MSHAmphetamineMC4R protein, mouseMelanocortinsPro-OpiomelanocortinReceptor, Melanocortin, Type 4amphetamineBATblood pressurebody weightcardiovascularenergy expenditurefood intakehypertensionMC4Rmelanocortin systemobesitythermogenesisweight loss

Identifiers

PMID39914386
PMCPMC11866487

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.