GEO series

An unimolecular GIPR:GLP-1R:PPAR , , quintuple agonist eliminates obesity and insulin resistance in mice.

GSE314029 Mus musculus (mouse) RNA-seq (gene expression) 159 samples Submitted 2026/02/14 Platform GPL24247

At a glance

RNA-seq (gene expression) · mouse · 159 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: 159 samples
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: GLP-1R-GIPR-PPARα/γ/δ quintuple agonism corrects obesity and diabetes in miceNature · 2026

Summary (written by the submitters)

Drugs to improve obesity-linked metabolic dysfunction are on the rise, with GLP-1:GIP co-agonism being effective in the management of obesity and type 2 diabetes, and with Lanifibranor (Lani), a nuclear acting small molecule triple agonist at the peroxisome proliferator-activated receptors alpha, gamma and delta (PPAR , , ) being in phase 3 development for the treatment of metabolic dysfunction-associated steatohepatitis.

Read the full summary ↓

Seeking to further improve the metabolic efficacy of GLP-1:GIP co-agonism, we here report the design and preclinical evaluation of an unimolecular quintuple agonist, which synergistically combines the body weight and blood glucose lowering effects of GLP-1:GIP co-agonism with the insulin sensitizing effects of Lani through its targeted delivery into only cells that express the receptor for either GIP or GLP-1. In vitro, GLP-1:GIP:Lani is indistinguishable from its GLP-1:GIP backbone in GIPR and GLP-1R signaling and equally stimulates insulin secretion in isolated murine islets. In vivo, however, GLP-1:GIP:Lani is much superior to GLP-1:GIP co-agonism or Semaglutide to decrease body weight, food intake, and hyperglycemia in obese and insulin resistant mice through synergistic incretin and PPAR action in key glucoregulatory tissues. The superior metabolic action of GLP-1:GIP:Lani is demonstrated in mice with genetic (db/db) and diet-induced obesity (DIO), is accelerated in DIO mice with adipose-specific overexpression of GIPR and is absent in DIO double-incretin receptor knock-out mice. Collectively, our data suggest that this novel quintuple polyagonist holds unprecedented therapeutic value to treat obesity and type 2 diabetes.

Published in

GLP-1R-GIPR-PPARα/γ/δ quintuple agonism corrects obesity and diabetes in mice

Liskiewicz D, Novikoff A, Khalil A et al. · Nature 2026 · PMID 42056522 · doi:10.1038/s41586-026-10427-5

This dataset

Open GSE314029 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 GSE314029_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 PRJNA1372460 and SRA study SRP650730. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 42056522) ↗

Samples in this study

The sample list for this study is not cached yet. Press Load samples and it will be fetched from NCBI.

+ 159 more — browse all 159 samples with per-sample file links →

Datasets on a similar topic

GSE293291 GIPR-Ab/GLP-1 Peptide-antibody Conjugate Requires CNS GIPRs and GLP-1Rs to Engage Anorexigenic Circuitry for Additive Weight Loss in Obese Mice 60 samples shares glp-1r, gipr
GSE184855 PPAR agonist, DTMB reduces chronic neuroinflammation in 5xFAD mice model. 22 samples shares ppar, agonist
GSE266899 The GLP-1R agonist semaglutide reshapes pancreatic cancer associated fibroblasts reducing collagen hydroxyprolination and favoring immune infiltration. 18 samples shares glp-1r, agonist
GSE328680 Hepatocyte-specific PPARγ Deletion Uncovers Role of an Antagonistic PPARγ–HNF4α Transcriptional Axis in MASLD Progression 12 samples shares ppar, agonist
GSE297484 An aerosolised dual-action Autotaxin inhibitor-PPARγ agonist for the treatment of pulmonary fibrosis. 9 samples shares ppar, agonist
GSE312718 Pharmacokinetics and tissue distribution of dual PPARα/γ agonist gigantol in mice 6 samples shares ppar, agonist
GSE11805 PPARdelta ligand GW1516, AMPK agonist AICAR, and exercise training 24 samples shares ppar, agonist
GSE35011 PPARg agonists induce a white-to-brown fat conversion through stabilization of PRDM16 protein 8 samples shares ppar, agonist

Search all mouse RNA-seq datasets in GEO →

Share this dataset

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.