Evidence map›Paper›PMID 40449730›Full record

ArticleMolecular metabolism2025

Uncovering the role of Gpr45 in obesity regulation.

Eva O Karolczak, Chia Li, Ivan C Alcantara, Isabel M Cohen, Claire Gao, Cuiying Xiao, Abigail I Goldschmidt, Cynthia A Pinkus, Junjie Li, Monica M Li and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular metabolism, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. 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

15 authors.

Eva O KarolczakDiabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
Chia LiDiabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
Ivan C AlcantaraDiabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA; NIH-Brown University Graduate Program in Neuroscience, Bethesda, MD, USA.
Isabel M CohenDiabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
Claire GaoDiabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
Cuiying XiaoDiabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
Abigail I GoldschmidtDiabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
Cynthia A PinkusInternal Medicine Research Unit, Pfizer Inc., Cambridge MA, USA.
Junjie LiInternal Medicine Research Unit, Pfizer Inc., Cambridge MA, USA.
Monica M LiInternal Medicine Research Unit, Pfizer Inc., Cambridge MA, USA.
Ryan M EsquejoInternal Medicine Research Unit, Pfizer Inc., Cambridge MA, USA.
Jean-Philippe FortinInternal Medicine Research Unit, Pfizer Inc., Cambridge MA, USA.
Kendra K BenceInternal Medicine Research Unit, Pfizer Inc., Cambridge MA, USA.
Marc L ReitmanDiabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
Michael J KrashesDiabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA. Electronic address: michael.krashes@nih.gov.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectivesG protein-coupled receptors (GPCRs) are the most druggable targets in biology due to their cell-type specificity, ligand binding, and cell surface accessibility. Underscoring this, agonists for GPCRs have recently revolutionized the treatment of diabetes and obesity. The rampant success of these compounds has invigorated interest in identifying additional GPCRs that modulate appetite and body weight homeostasis. One such potential therapeutic target is G-protein couped receptor 45 (Gpr45), an orphan GPCR expressed both centrally and peripherally. We aimed to explore the role of Gpr45 as well as neurons expressing Gpr45 in energy balance.

methodsThree novel transgenic mouse models were engineered to investigate the functional contribution of Gpr45 to body weight and appetite regulation: 1) a global Gpr45 knockout, 2) a conditional floxed Gpr45 allele, and 3) a Gpr45-CreERT2 knock-in. Metabolic profiling was performed in global Gpr45 knockout animals including body weight, food intake, body mass, energy expenditure, and body temperature measurements. Animals harboring a conditional floxed Gpr45 allele were bred to mice expressing Cre-recombinase in excitatory neurons labeled via Vesicular glutamate transporter 2 (Vglut2), inhibitory cells expressing Vesicular GABA transporter (Vgat), or neurons marked by the transcription factor Single-minded 1 (Sim1) and monitored for body weight and food consumption. Additionally, floxed Gpr45 mice were bilaterally injected with AAV-Cre targeting the paraventricular nucleus of the hypothalamus (PVH) and body weight and food intake were evaluated. The Gpr45-CreERT2 knock-in model was used to express chronic and acute actuators to the PVH to assess the role of PVH

resultsGlobal Gpr45 disruption caused marked weight gain, increased food intake and fat mass, but no detectable alterations in core temperature or energy output. Selective deletion of Gpr45 from Sim1+ or excitatory Vglut2+ but not inhibitory Vgat+, neurons produced obesity and hyperphagia. Targeted deletion of Gpr45 from the PVH phenocopies these metabolic changes suggesting a major site of action of Gpr45 signaling is glutamatergic neurons residing in the PVH. Tetanus toxin light chain (TeNT) was used to permanently silence PVH

conclusionsGpr45 is a putative therapeutic candidate that could be targeted to combat obesity and overeating.

Indexed as

ObesityReceptors, G-Protein-CoupledAnimalsBody WeightEatingEnergy MetabolismFemaleMaleMiceMice, Inbred C57BLMice, KnockoutMice, TransgenicNeuronsReceptors, G-Protein-Coupledbehavioral neurosciencebody weight regulationfood intakeG protein-coupled receptor 45

Identifiers

PMID40449730
PMCPMC12205348

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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 OpenQuestion graph.