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Whole body MondoA deletion protects against diet-induced obesity through uncontrolled multi-organ substrate utilization and futile cycling

GSE303998 Mus musculus (mouse) RNA-seq (gene expression) 40 samples Submitted 2026/02/18 Platform GPL19057Platform GPL24247
At a glance

RNA-seq (gene expression) · mouse · 40 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
40 samples: 8 conditions, mostly with about 6 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
Whole body MondoA deletion protects against diet-induced obesity through uncontrolled multi-organ substrate utilization and futile cyclingbioRxiv : the preprint server for biology · 2025
Summary (written by the submitters)
Objective – Delineating the nodal control points that maintain whole-body energy homeostasis is critical for understanding potential treatments of obesity and cardiometabolic diseases. The nutrient-sensing transcription factor MondoA is a regulator of skeletal muscle fuel storage, where muscle-specific inhibition improves glucose tolerance and insulin sensitivity.
Read the full summary ↓
However, the role of MondoA in whole body energy metabolic homeostasis is not understood. Methods – Generalized MondoA knockout (gKO) mice were generated and assessed for glucose tolerance and insulin sensitivity, body composition, energy expenditure, cold tolerance, and tissue specific transcriptional changes in response to high fat diet. Complementary studies in cultured human adipocytes assessed the impact of MondoA deficiency on substrate utilization and lipolysis. Results – gKO mice are protected from diet-induced obesity and insulin resistance, through increased whole body energy expenditure. gKO mice exhibit reduced brown and inguinal white adipose tissue mass, without evidence of beiging. The gKO mice are hyperlactemic and isolated MondoA-deficient adipocytes have increased 2-deoxyglucose uptake and glycolytic function. Lastly, gKO mice and KO adipocytes display increased circulating glycerol relative to free fatty acids in response to adrenergic stimulus consistent with elevated re-esterification. This phenotype is not recapitulated in adipose-specific KO mice. Conclusions – MondoA deficiency alters cellular sensing of nutrient availability and storage/utilization mechanisms. In the whole-body setting, this results in increased energy expenditure, potentially related to increased glucose uptake, glycolytic flux, and glycerol synthesis to supply high rates of lipolysis and lipid re-esterification. These results suggest that MondoA functions to maintain fuel storage and when lost, inter-organ futile fuel cycling ensues.
Published in
Whole body MondoA deletion protects against diet-induced obesity through uncontrolled multi-organ substrate utilization and futile cycling
Berger JH, Lau AN, James LC et al. · bioRxiv : the preprint server for biology 2025 · PMID 41279368 · doi:10.1101/2025.10.06.680559
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 GSE303998_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 PRJNA1298600 and SRA study SRP604753. Searching any of these in the dataset finder brings you back here.

Study design
8 conditions, mostly with about 6 replicates each
iWAT MondoAKO Chow Diet ×6 iWAT WT High Fat Diet ×6 iWAT MondoAKO High Fat Diet ×6 iWAT WT Chow Diet ×6 BAT WT Chow Diet ×4 BAT WT High Fat Diet ×4 BAT MondoAKO High Fat Diet ×4 BAT MondoAKO Chow Diet ×4

Supports a between-group comparison across 40 samples.

How we read this: 8 replicated groups read from 40 sample titles; they account for 40 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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