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ChREBP-mediated control of Them1 expression coordinates thermogenesis with glycolysis and lipogenesis

GSE280981 Mus musculus (mouse) RNA-seq (gene expression) 26 samples Submitted 2025/02/19 Platform GPL21103
At a glance

RNA-seq (gene expression) · mouse · 26 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
26 samples: 26 samples, each with a distinct title — no replicated groupsGroups 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
ChREBP-mediated up-regulation of Them1 coordinates thermogenesis with glycolysis and lipogenesis in response to chronic stressScience signaling · 2024
Summary (written by the submitters)
Activation of thermogenic brown adipose tissue (BAT) and inducible beige adipose tissue (BeAT) is triggered by environmental or metabolic stimuli, including cold ambient temperatures and nutrient stress. Thioesterase superfamily member 1 (Them1), a long chain fatty acyl-CoA thioesterase that is enriched in BAT, suppresses acute cold-induced thermogenesis.
Read the full summary ↓
Here, we demonstrate that Them1 expression was induced in BAT and BeAT by the carbohydrate response element binding protein (ChREBP) in response to chronic cold exposure or to the activation of the integrated stress response (ISR). Under either condition, Them1 suppressed energy expenditure. Consequently, mice lacking Them1 in BAT and BeAT exhibited resistance to obesity and glucose intolerance induced by feeding with a high-fat diet. During chronic cold exposure or ISR activation, Them1 accumulated in the nucleus, where it interacted with ChREBP and reduced the expression of its target genes, including those encoding enzymes that mediate glycolysis and de novo lipogenesis. These findings demonstrate that in response to chronic cold- or nutrient-induced stress, the induction of Them1 by ChREBP limits thermogenesis while coordinately reducing glucose utilization and lipid biosynthesis through its distinct activities in the cytoplasm and nucleus. Targeted inhibition of Them1 may represent a potential therapeutic approach to increase the activity of BAT and BeAT to enhance energy expenditure in the management of obesity-associated metabolic disorders.
Published in
ChREBP-mediated up-regulation of Them1 coordinates thermogenesis with glycolysis and lipogenesis in response to chronic stress
Xu X, Mendoza A, Krumm CS et al. · Science signaling 2024 · PMID 39626011 · doi:10.1126/scisignal.adk7971
This dataset
Open GSE280981 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 GSE280981_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 PRJNA1181773 and SRA study SRP542995. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39626011) ↗
Study design
26 samples, each with a distinct title — no replicated groups

Any grouping that defines a comparison lives in the sample characteristics, which GEO records separately from the titles.

How we read this: Read from 26 sample titles: 26 distinct titles with little repetition. 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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