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GIPR-Ab/GLP-1 Peptide-antibody Conjugate Requires CNS GIPRs and GLP-1Rs to Engage Anorexigenic Circuitry for Additive Weight Loss in Obese Mice

GSE293291 Mus musculus (mouse) RNA-seq (gene expression) 60 samples Submitted 2025/04/29 Platform GPL34328
At a glance

RNA-seq (gene expression) · mouse · 60 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
60 samples: 12 conditions, mostly with about 5 replicates eachGroups 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
GIPR-Ab/GLP-1 peptide-antibody conjugate requires brain GIPR and GLP-1R for additive weight loss in obese miceNature metabolism · 2025
Summary (written by the submitters)
Glucose-dependent insulinotropic polypeptide receptor (GIPR) and glucagon-like peptide 1 receptor (GLP-1R) are expressed in the central nervous system (CNS) and regulate food intake. Here, we demonstrate that a peptide-antibody conjugate that blocks GIPR while simultaneously activating GLP-1R (GIPR-Ab/GLP-1) requires both CNS GIPR and CNS GLP-1R for additive effects on body weight loss in obese, primarily male, mice.
Read the full summary ↓
Moreover, dulaglutide produces greater weight loss in CNS GIPR KO mice compared to WT mice, and the extent of weight loss achieved with dulaglutide + GIPR-Ab is attenuated in CNS GIPR KO mice. WT mice treated with GIPR-Ab/GLP-1 or CNS GIPR KO mice exhibit similar changes in gene expression related to tissue remodeling, lipid metabolism, and inflammation in white adipose tissue and liver. Moreover, GIPR-Ab/GLP-1 is detected in circumventricular organs in the brain and activates c-FOS in downstream neural substrates involved in appetite regulation. Hence, both CNS GIPR and GLP-1R signaling are required for the full effect of a GIPR-Ab/GLP-1 peptide-antibody conjugate, with loss of CNS GIPR activity potentiating the actions of GLP-1R agonism.
Published in
GIPR-Ab/GLP-1 peptide-antibody conjugate requires brain GIPR and GLP-1R for additive weight loss in obese mice
Liu CM, Killion EA, Hammoud R et al. · Nature metabolism 2025 · PMID 40301582 · doi:10.1038/s42255-025-01295-w
This dataset
Open GSE293291 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 GSE293291_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 PRJNA1243925 and SRA study SRP574863. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40301582) ↗
Study design
12 conditions, mostly with about 5 replicates each
Glp1rfl/fl Vehicle, Liver, biol ×5 Glp1rWnt1-/- Vehicle, Liver, biol ×5 Glp1rfl/fl mGIPR-Ab/P1, Liver, biol ×5 Glp1rfl/fl Vehicle, Inguinal White Adipose, b… ×5 Glp1rWnt1-/- Vehicle, Inguinal White Adipose,… ×5 Glp1rfl/fl mGIPR-Ab/P1, Inguinal White Adipos… ×5 Giprfl/fl Vehicle, Liver, biol ×5 GiprSyn-/- Vehicle, Liver, biol ×5 +4 more

Supports a between-group comparison across 60 samples.

How we read this: 12 replicated groups read from 60 sample titles; they account for 60 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

+ 20 more — browse all 60 samples with per-sample file links →

Datasets on a similar topic

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Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.