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Study · Not a test of the peptide alone · 2023

2 results

Obesity medication lorcaserin activates brainstem GLP-1 neurons to reduce food intake and augments GLP-1 receptor agonist induced appetite suppression.

Wagner S, Brierley DI, Leeson-Payne A, Jiang W, Chianese R, Lam BYH, Dowsett GKC, Cristiano C, Lyons D, Reimann F, Gribble FM, Martinez de Morentin PB, Yeo GSH, Trapp S, Heisler LK

Molecular metabolism30 Dec 2022Cited by 30 (Europe PMC)

PMID36592795 (opens in a new tab)PMCIDPMC9841057 (opens in a new tab)DOI10.1016/j.molmet.2022.101665 (opens in a new tab)PepBankPUB-36592795
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Summary

ObjectiveOverweight and obesity are endemic in developed countries, with a substantial negative impact on human health. Medications developed to treat obesity include agonists for the G-protein coupled receptors glucagon-like peptide-1 (GLP-1R; e.g. liraglutide), serotonin 2C (5-HT2CR; e.g, lorcaserin), and melanocortin4 (MC4R) which reduce body weight primarily by suppressing food intake. However, the mechanisms underlying the therapeutic food intake suppressive effects are still being defined and were investigated here.MethodsWe profiled PPG neurons in the nucleus of the solitary tract (PPGNTS) using single nucleus RNA sequencing (Nuc-Seq) and histochemistry. We next examined the requirement of PPGNTS neurons for obesity medication effects on food intake by virally ablating PPGNTS neurons. Finally, we assessed the effects on food intake of the combination of liraglutide and lorcaserin.ResultsWe found that 5-HT2CRs, but not GLP-1Rs or MC4Rs, were widespread in PPGNTS clusters and that lorcaserin significantly activated PPGNTS neurons. Accordingly, ablation of PPGNTS neurons prevented the reduction of food intake by lorcaserin but not MC4R agonist melanotan-II, demonstrating the functional significance of PPGNTS 5-HT2CR expression. Finally, the combination of lorcaserin with GLP-1R agonists liraglutide or exendin-4 produced greater food intake reduction as compared to either monotherapy.ConclusionsThese findings identify a necessary mechanism through which obesity medication lorcaserin produces its therapeutic benefit, namely brainstem PPGNTS neurons. Moreover, these data reveal a strategy to augment the therapeutic profile of the current frontline treatment for obesity, GLP-1R agonists, via coadministration with 5-HT2CR agonists.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study2

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

Studies that did not test the peptide alone2

In this study, the peptide 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 the peptide.

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

    In animals, ablation of PPG-NTS neurons did not prevent the reduction of food intake by the MC4R agonist melanotan II, unlike the effect of lorcaserin.

    In plain wordsIn animals, removing PPG-NTS neurons did not stop melanotan II from reducing food intake.

    Peptide
    Melanotan II
    Outcome
    No significant changeEffect of PPG-NTS neuron ablation on MTII food intake reduction
    Study

    n: not reported in source

    Outcome group
    Appetite and food intake · Metabolic and weight

    Source sentences

    Summary
    ablation of PPGNTS neurons prevented the reduction of food intake by lorcaserin but not MC4R agonist melanotan-II, demonstrating the functional significance of PPGNTS 5-HT2CR expression.
    1 context sentence
    Summary · context
    We next examined the requirement of PPGNTS neurons for obesity medication effects on food intake by virally ablating PPGNTS neurons.

    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 Liraglutide aloneAnimal study (in vivo)Efficacy outcome

    In animals, the combination of lorcaserin with the GLP-1R agonists liraglutide or exendin-4 reduced food intake more than either monotherapy.

    In plain wordsIn animals, lorcaserin combined with GLP-1 agonists such as liraglutide cut food intake more than either drug alone.

    Peptide
    Liraglutide
    Outcome
    DecreaseFood intake with lorcaserin plus GLP-1R agonist
    Study

    n: not reported in source

    Comparator
    Either monotherapy
    Outcome group
    Appetite and food intake · Metabolic and weight

    Source sentences

    Summary
    Finally, the combination of lorcaserin with GLP-1R agonists liraglutide or exendin-4 produced greater food intake reduction as compared to either monotherapy.
    1 context sentence
    Summary · context
    Finally, we assessed the effects on food intake of the combination of liraglutide and lorcaserin.

    In this study, Liraglutide 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 Liraglutide.

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 3Current

    10 Oct 2026, 09:43 UTC

    Study results updated

  2. Version 2

    9 Oct 2026, 03:05 UTC

    Study data updated · source update from Europe PMC

  3. 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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