Evidence map›Paper›PMID 40700519›Full record

ArticleScience translational medicine2025

Hindbrain octadecaneuropeptide gliotransmission as a therapeutic target for energy balance control without nausea or emesis.

Caroline E Geisler, Kylie S Chichura, Oleksandr Orativskyi, Jiayin Hu, Drew L Belser, Caitlyn M Pelletier, Tito Borner, Caitlin Baumer-Harrison, Bart C De Jonghe, Richard C Crist and 3 more

Abstract read
In one paragraph

Article in Science translational 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. Article
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.

Caroline E GeislerDepartment of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0002-4790-7000
Kylie S ChichuraDepartment of Chemistry, Syracuse University, Syracuse, NY, USA.
Oleksandr OrativskyiDepartment of Chemistry, Syracuse University, Syracuse, NY, USA.ORCID 0009-0006-6339-9460
Jiayin HuDepartment of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Drew L BelserDepartment of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0009-0007-2068-9342
Caitlyn M PelletierDepartment of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0002-2214-2830
Tito BornerDepartment of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0001-9438-695X
Caitlin Baumer-HarrisonDepartment of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0002-6287-5887
Bart C De JongheDepartment of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0002-6980-5355
Richard C CristDepartment of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0001-9461-1256
Benjamin C ReinerDepartment of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0001-7796-587X
Robert P DoyleDepartment of Chemistry, Syracuse University, Syracuse, NY, USA.ORCID 0000-0001-6786-5656
Matthew R HayesDepartment of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0001-9782-6551

Funding

Neural Mechanisms of Nausea, Vomiting, and Energy DysregulationR01DK112812 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI Bart C DE JONGHE, MATTHEW R HAYES · 2017 to 2026
$4.4M
Indirect calorimetry cages equipped for glucose and blood pressure telemetryS10OD025098 · OD · UNIVERSITY OF PENNSYLVANIA · PI BAUR, JOSEPH A. · 2019 to 2019
$750k
Vagal REV-ERB as a Circadian Regulator of Satiation SignalingF32DK127591 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI GEISLER, CAROLINE ELYSE · 2021 to 2023
$215k
NIDDK NIH HHS F32 DK127591NIDDK NIH HHS R01 DK112812NIH HHS S10 OD025098
6 · The paper itself

Abstract

Glia play a dynamic role in central nutrient sensing and appetite regulation yet represent underexplored targets in treating dysregulated energy balance. Glia within the dorsal vagal complex of the hindbrain synthesize the anorexigenic peptide octadecaneuropeptide (ODN), the influence and therapeutic potential of which remain to be explored. We demonstrate that hindbrain-targeted ODN induced weight loss, counteracted glucoprivation, and improved glucose clearance in rats. Furthermore, blocking central ODN signaling attenuated the anorectic response to GLP-1R agonists in rats. Peripheral administration of an ODN derivative, TDN, improved insulin sensitivity assessed by hyperinsulinemic-euglycemic clamp in obese mice and induced weight loss without pica behavior, a proxy for nausea in rats, or emesis in the musk shrew, a vomiting mammalian model. Central ODN and TDN treatment in rats was not accompanied by changes in core body temperature, physical activity, or heart rate. This work highlights hindbrain ODN signaling as an important modulator of energy balance and demonstrates the potential for targeting this gliopeptide system to treat dysregulated feeding and metabolic activity without side effects.

Indexed as

Energy MetabolismNauseaNeuropeptidesRhombencephalonVomitingAnimalsGlucoseMaleMiceRatsRats, Sprague-DawleyShrewsSignal TransductionWeight LossGlucoseNeuropeptides

Identifiers

PMID40700519
PMCPMC12980401

What Socratic holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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 Socratic graph.