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Glucagon controls obesity-specific energy expenditure via persistent cAMP/PKA signaling [RNA-Seq 1]

GSE291380 Mus musculus (mouse) RNA-seq (gene expression) 16 samples Submitted 2025/06/23 Platform GPL24247
At a glance

RNA-seq (gene expression) · mouse · 16 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
16 samples: 4 × wt-treated vs 4 × ko-treated vs 4 × wt-control vs 4 × ko-controlGroups 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.
Summary (written by the submitters)
Background & Aims: Glucagon (GCG) analogues are gaining attention as promising components in incretin-based therapeutics for obesity and metabolic dysfunction-associated steatohepatitis. However, the biology of chronic glucagon treatment, in particular, the molecular underpinnings of GCG-induced energy expenditure and lipid metabolism, remain poorly defined.
Read the full summary ↓
Methods: We utilized a long-acting GCG analogue (LA-GCG) in conjunction with hepatic and adipose glucagon receptor knockout mouse models. Through an integrative approach that combined metabolic, biochemical and omics techniques, we investigated the molecular mechanisms underlying GCG-induced energy expenditure and metabolic benefits. Results: We demonstrate that the LA-GCG enhances energy expenditure in diet-induced obese mice with an essential role of hepatic, but not adipose, GCGR signaling. Intriguingly, the enhancement in energy expenditure is observed only in obese but not in lean mice. The preferential efficacy is plausibly found in a prolonged activation of cAMP/PKA signaling through PDE4B/4D downregulation by LA-GCG. Conversely, the cAMP/PKA signaling is promptly attenuated by the PDE4B/4D activity in lean mice. Interestingly, unlike the EE phenotype, the lipid-clearing capacity of LA-GCG is independent of the PDE4/cAMP/PKA axis. Conclusions: These findings provide the molecular basis for GCG-induced energy expenditure and metabolic benefits and suggest the phenotypic segregation of cAMP/PKA-dependent and independent effects.
This dataset
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.

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 GSE291380_RAW.tar (it can run to tens of gigabytes).

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.

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 PRJNA1233269 and SRA study SRP568721. Searching any of these in the dataset finder brings you back here.

Study design
4 × wt-treated vs 4 × ko-treated vs 4 × wt-control vs 4 × ko-control

Supports a case/control comparison: 4 samples read as cases, 8 as controls.

How we read this: 4 replicated groups read from 16 sample titles; they account for 16 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
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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.