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Exposure of Ldlr-/- mice to a PFAS mixture increased circulating cholesterol and decreased bile acid excretion with concurrent increases in male ileal ASBT

GSE263158 Mus musculus (mouse) RNA-seq (gene expression) 20 samples Submitted 2024/08/14 Platform GPL24247

At a glance

RNA-seq (gene expression) · mouse · 20 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: 20 samples: 10 × Ileum, male, control, vs 8 × Ileum, male, PFAS, vs 2 × Ileum, male PFAS,Groups 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: Previous epidemiological studies have repeatedly found per- and polyfluoroalkyl substances (PFAS) exposure associated with higher circulating cholesterol, one of the greatest risk factors for development of coronary artery disease. The main route of cholesterol catabolism is through its conversion to bile acids, which circulate between the liver and ileum via enterohepatic circulation.

Read the full summary ↓

Patients with coronary artery disease have decreased bile acid excretion, indicating that PFAS-induced changes of enterohepatic circulation may play a critical role in cardiovascular risk. Objectives: Using a mouse model with high LDL-VLDL cholesterol and aortic lesion development similar to humans, the current study investigates mechanisms linking exposure to a PFAS mixture with increased cholesterol. Methods: Male and female Ldlr-/- mice were fed an atherogenic diet (Clinton/Cybulsky low fat, 0.15% cholesterol) and exposed to a mixture of 5 PFAS representing legacy, replacement, and emerging subtypes (i.e., PFOA, PFOS, PFNA, PFHxS, GenX), each at a concentration of 2 mg/L, for 7 weeks. Blood was collected longitudinally for cholesterol measurements and mass spectrometry was used to measure circulating and fecal bile acids. Transcriptomic analysis of ileal samples was performed via RNA-sequencing. Results: After 7 weeks of PFAS exposure, average circulating PFAS levels were measured at 21.6, 20.1, 31.2, 23.5, and 1.5 µg/mL in PFAS-exposed females and 12.9, 9.7, 23, 14.3, and 1.7 µg/mL in PFAS-exposed males for PFOA, PFOS, PFHxS, PFNA, and GenX, respectively. PFAS exposure led to elevated circulating cholesterol levels after 7 weeks compared to vehicle mice, with females increasing 18% and males increasing 24%. Total circulating bile acid levels were elevated in PFAS-exposed mice by 230% in males and 290% in females compared to vehicle. PFAS decreased fecal bile acid levels by 62% in females and 59% in males. In the ileum, expression levels of the bile acid reuptake transporter ASBT were increased due to PFAS exposure. Discussion: Mice exposed to a PFAS mixture display increased circulating cholesterol and bile acids perhaps due to changes in enterohepatic circulation. This study implicates PFAS-mediated effects at the site of the ileum as a possible critical mediator of increased cardiovascular risk due to PFAS.

This dataset

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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 GSE263158_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 PRJNA1095993 and SRA study SRP499607. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗

Study design

10 × Ileum, male, control, vs 8 × Ileum, male, PFAS, vs 2 × Ileum, male PFAS,

Supports a between-group comparison across 20 samples.

How we read this: 3 replicated groups read from 20 sample titles; they account for 20 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

GSM8186943 Ileum, male, control, rep1 Ileum, male, control,
GSM8186944 Ileum, male, control, rep2 Ileum, male, control,
GSM8186945 Ileum, male, control, rep3 Ileum, male, control,
GSM8186946 Ileum, male, control, rep4 Ileum, male, control,
GSM8186947 Ileum, male, control, rep5 Ileum, male, control,
GSM8186948 Ileum, male, control, rep6 Ileum, male, control,
GSM8186949 Ileum, male, control, rep7 Ileum, male, control,
GSM8186950 Ileum, male, control, rep8 Ileum, male, control,
GSM8186951 Ileum, male, control, rep9 Ileum, male, control,
GSM8186952 Ileum, male, control, rep10 Ileum, male, control,
GSM8186953 Ileum, male, PFAS, rep1 Ileum, male, PFAS,
GSM8186954 Ileum, male PFAS, rep2 Ileum, male PFAS,
GSM8186955 Ileum, male PFAS, rep3 Ileum, male PFAS,
GSM8186956 Ileum, male, PFAS, rep4 Ileum, male, PFAS,
GSM8186957 Ileum, male, PFAS, rep5 Ileum, male, PFAS,
GSM8186958 Ileum, male, PFAS, rep6 Ileum, male, PFAS,
GSM8186959 Ileum, male, PFAS, rep7 Ileum, male, PFAS,
GSM8186960 Ileum, male, PFAS, rep8 Ileum, male, PFAS,
GSM8186961 Ileum, male, PFAS, rep9 Ileum, male, PFAS,
GSM8186962 Ileum, male, PFAS, rep10 Ileum, male, PFAS,

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