GEO series

Endothelial Cell-specific Activation of NOX1 Drives Obesity and Metabolic Syndrome via Skeletal Muscle Mitochondrial Dysfunction with Novel Genetic Signatures

GSE316731 Mus musculus (mouse) RNA-seq (gene expression) 12 samples Submitted 2026/01/20 Platform GPL21493

At a glance

RNA-seq (gene expression) · mouse · 12 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: 12 samples: 12 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.

Summary (written by the submitters)

Presently, we investigated hypothesized roles and mechanisms of cell type-specific, selective activation of different vascular NADPH oxidase (NOX) isoforms in obesity and metabolic syndrome. Expression of NOX1 was significantly upregulated in WT mice fed high-fat diet. Global knockout of NOX1 (NOX1-/y), rather than of NOX2/NOX4, markedly abrogated high-fat feeding induced body weight/fat mass gain, preadipocyte differentiation, fatty liver, glucose intolerance, and insulin/leptin resistance.

Read the full summary ↓

Intriguingly, endothelial-specific NOX1 knockout (Cdh5cre-NOX1CKO), rather than vascular smooth muscle-specific NOX1 knockout (Myh11cre-NOX1CKO), substantially alleviated these features of obesity and metabolic syndrome. Consistently, endothelial-specific NOX1 knockin mice (Cdh5cre-NOX1CKI) fed high-fat diet displayed exaggerated metabolic disorders. Endothelial cell (EC)-specific knockout/knockin of NOX1 was confirmed using EC washout experiments. Food/water intakes were not different from corresponding controls in high-fat fed NOX1-/y, Cdh5cre-NOX1CKO or Cdh5cre-NOX1CKI mice, indicating no difference in energy intake. Instead, spontaneous activity, exercise capacity, mitochondrial oxygen consumption/ATP production, skeletal muscle mitochondrial function (ROS production and swelling activity), and mitochondrial cristae structure were all substantially improved in NOX1-/y or Cdh5cre-NOX1CKO mice, indicating augmented energy expenditure attributed to preserved skeletal muscle mitochondrial function. Supportively, Cdh5cre-NOX1CKI mice displayed deteriorated exercise capacity and skeletal muscle mitochondrial dysfunction. Endothelium-dependent vasorelaxation was restored in high-fat fed NOX1-/y or Cdh5cre-NOX1CKO mice, confirming improved endothelial function. RNA-seq identified 4 genes (Cntnap4, Sgsm1, Tll2 and Syt9) and 7 genes (Odf3l2, Col9a1, Cldn23, Atp5g2, Nkx6-3, Ntsr2 and Zfp69) significantly down/upregulated in high-fat fed Cdh5cre-NOX1CKO mice, among which Cntnap4 and COL9A1 linked to muscular disorders. Importantly, we observed marked upregulation of NOX1 in isolated coronary arteries from human obese patients. Taken together, our data for the first time establish a novel and paradigm-shifting concept that endothelial NOX1 drives systematic metabolic phenotypes, via impairment in skeletal muscle mitochondrial dysfunction with novel genetic signatures. Tissue-specific targeting of endothelial NOX1 and novel candidate genes may prove to be robustly effective in treating obesity and metabolic syndrome.

This dataset

Open GSE316731 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 GSE316731_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 PRJNA1404098 and SRA study SRP663458. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗

Study design

12 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 12 sample titles: 12 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

GSM9459070 #971, soleus muscles, Cdh5cre-WT mice, chow diet
GSM9459071 #1088, soleus muscles, Cdh5cre-WT mice, chow diet
GSM9459072 #1009, soleus muscles, Cdh5cre-WT mice, chow diet
GSM9459073 #969, soleus muscles, Cdh5Cre-NOX1CKO, chow diet
GSM9459074 #1089, soleus muscles, Cdh5Cre-NOX1CKO, chow diet
GSM9459075 #970, soleus muscles, Cdh5Cre-NOX1CKO, chow diet
GSM9459076 #1133, soleus muscles, Cdh5cre-WT mice, high fat diet
GSM9459077 #1200, soleus muscles, Cdh5cre-WT mice, high fat diet
GSM9459078 #1185, soleus muscles, Cdh5cre-WT mice, high fat diet
GSM9459079 #1134, soleus muscles, Cdh5Cre-NOX1CKO, high fat diet
GSM9459080 #1201, soleus muscles, Cdh5Cre-NOX1CKO, high fat diet
GSM9459081 #1270, soleus muscles, Cdh5Cre-NOX1CKO, high fat diet

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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.