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Linear ubiquitination prevents lipodystrophy and obesity-associated metabolic syndrome

GSE298555 Mus musculus (mouse) RNA-seq (gene expression) 19 samples Submitted 2025/08/22 Platform GPL24247
At a glance

RNA-seq (gene expression) · mouse · 19 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
19 samples: 5 × Liver, Hoip_fl/fl.AdipoQ.Cre_positive, 16 weeks HFD 60%, biol vs 5 × Liver, Hoip_fl/fl.AdipoQ.Cre_negative, 16 weeks HFD 60%, biol vs 5 × Liver, Hoip_fl/fl.AdipoQ.Cre_negative, 16 weeks CD 14%, biol vs 4 × Liver, Hoip_fl/fl.AdipoQ.Cre_positive, 16 weeks CD 14%, biolGroups 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
Linear ubiquitination prevents lipodystrophy and obesity-associated metabolic syndromeScience advances · 2025
Summary (written by the submitters)
Adipocyte hypertrophy during obesity triggers chronic inflammation, leading to metabolic disorders. However, the role of adipocyte-specific inflammatory signalling in metabolic syndrome remains unclear. The linear ubiquitin chain assembly complex, LUBAC, is an E3-ligase that generates non-degradative linear ubiquitination (Lin-Ub). LUBAC regulates NF-κB/MAPK-driven inflammation and prevents cell death triggered by immune receptors like TNF-receptor-1.
Read the full summary ↓
Here we show that mice lacking HOIP, LUBAC’s catalytic subunit, in adipocytes (HoipA-KO) display lipodystrophy and heightened susceptibility to obesity-induced metabolic syndrome, particularly Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). Mechanistically, loss of HOIP attenuates TNF-induced NF-κB activation and promotes cell death in human adipocytes. Inhibiting caspase-8-mediated cell death is sufficient to prevent lipodystrophy and MASLD in HoipA-KO obese mice. Importantly, HOIP expression in adipose tissue positively correlates with metabolic fitness in obese individuals. Overall, our findings reveal a fundamental developmental role for Lin-Ub in adipocytes by mitigating cell death-driven adipose tissue inflammation and protecting against obesity-related metabolic
Published in
Linear ubiquitination prevents lipodystrophy and obesity-associated metabolic syndrome
Hildebrandt X, Veli Ö, Hyoubi A et al. · Science advances 2025 · PMID 40961178 · doi:10.1126/sciadv.adw2539
This dataset
Open GSE298555 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 GSE298555_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 PRJNA1269933 and SRA study SRP589012. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40961178) ↗
Study design
5 × Liver, Hoip_fl/fl.AdipoQ.Cre_positive, 16 weeks HFD 60%, biol vs 5 × Liver, Hoip_fl/fl.AdipoQ.Cre_negative, 16 weeks HFD 60%, biol vs 5 × Liver, Hoip_fl/fl.AdipoQ.Cre_negative, 16 weeks CD 14%, biol vs 4 × Liver, Hoip_fl/fl.AdipoQ.Cre_positive, 16 weeks CD 14%, biol

Supports a between-group comparison across 19 samples.

How we read this: 4 replicated groups read from 19 sample titles; they account for 19 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
Datasets on a similar topic

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