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Cagrilintide lowers bodyweight through brain amylin receptors 1 and 3

GSE296488 Mus musculus (mouse) RNA-seq (gene expression) 116 samples Submitted 2025/06/05 Platform GPL24247
At a glance

RNA-seq (gene expression) · mouse · 116 samples

What it is
RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism
Mus musculus (mouse)
Samples
116 samples: 116 × p26688_28474/Groups are read from the sample names, not from the paper. Check the list below.
Data you can get
A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Paper
Cagrilintide lowers bodyweight through brain amylin receptors 1 and 3EBioMedicine · 2025
Summary (written by the submitters)
Amylin (AmyR) and calcitonin (CTR) receptor co-agonists are currently in Phase II/III clinical trials for obesity treatment. Amylin binds to a heterodimeric receptor composed of CTR and the receptor activity modifying proteins 1, 2 or 3 (RAMP1-3). We investigated the role of amylin 1 and 3 (AMY1R, AMY3R) receptors in modulating the pharmacological effects of the dual amylin–calcitonin receptor agonists, cagrilintide and salmon calcitonin (sCT), in RAMP1/3 knockout (KO) mice.
Read the full summary ↓
Male wild-type (WT) and KO littermate mice were fed high-fat diet for 23 weeks prior to the 3-week treatment period with vehicle, 150 nmol/kg sCT or 3 nmol/kg cagrilintide (SC, SID). Body weight loss was observed in WT cagrilintide-treated mice (-3.4 +/- 0.51 g, P<0.005; n=8/group), whereas sCT rather increased it (0.60 +/- 0.38 g, P<0.01; n=8/group). The absence of RAMP1 and RAMP3 impeded cagrilintide’s potency but improved sCT’s efficacy on weight loss. Cagrilintide and sCT both decreased food intake during the first few days of treatment in WT mice only (Day 1: veh 2.7 +/- 0.2 g; cagri 1.2 +/- 0.1 g, P<0.0001; sCT 1.5 +/- 0.2 g, P<0.0021; n=7-8/group). Both peptides activated cFos signal in neurons of the dorsal vagal complex (DVC) and lateral parabrachial nucleus (LPBN) of WT mice while AP cFos signal was decreased in cagrilintide-treated RAMP1/3 KO mice by 57% compared to WT cagrilintide-injected mice (P<0.001, n=5-6/group). Differential gene expression was analyzed in the DVC, LPBN and mediobasal hypothalamic area (MBH) of WT and RAMP1/3 KO mice. After 3 weeks of treatment, neither sCT nor cagrilintide significantly altered gene expression in the DVC or LPBN in WT mice. However, mRNA bulk sequencing points to a role of RAMP1/3 in synaptic function and receptor trafficking. Altogether, these results demonstrate the dependency of cagrilintide on AMY1R and AMY3R to lower body weight.
Published in
Cagrilintide lowers bodyweight through brain amylin receptors 1 and 3
Carvas AO, Leuthardt A, Kulka P et al. · EBioMedicine 2025 · PMID 40609154 · doi:10.1016/j.ebiom.2025.105836
This dataset
Open GSE296488 in finder → Find more mouse RNA-seq datasets →
Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓
2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE296488_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓
3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1259490 and SRA study SRP583381. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40609154) ↗
Study design
116 × p26688_28474/

Supports a between-group comparison across 116 samples.

How we read this: 1 replicated groups read from 116 sample titles; they account for 116 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study

+ 76 more — browse all 116 samples with per-sample file links →

Datasets on a similar topic

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