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Integrated Transcriptomic and Functional Dissection of Reversible Liver-Heart Dysfunction in a Preclinical MASLD-HFpEF Model

GSE304630 Mus musculus (mouse) RNA-seq (gene expression) 18 samples Submitted 2026/07/21 Platform GPL24247

At a glance

RNA-seq (gene expression) · mouse · 18 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: 18 samples: 6 conditions, mostly in triplicateGroups 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: A translational model of MASLD-associated HFpEF defines mitochondrial dysfunction and cardiac plasticity during disease progression and regressionMetabolism: clinical and experimental · 2026

Summary (written by the submitters)

Background Metabolic dysfunction-associated steatotic liver disease (MASLD) and its advanced form, MASH, are closely linked to cardiac dysfunction, particularly heart failure with preserved ejection fraction (HFpEF). However, the mechanisms underlying MASLD-associated HFpEF and its reversibility remain poorly understood, largely due to the lack of robust preclinical models.

Read the full summary ↓

Here, we established a translational model of MASLD-associated cardiac dysfunction that recapitulates the key features of human HFpEF. We applied functional and transcriptomic analyses of the left ventricle (LV) to define the pathways associated with cardiac dysfunction and its reversibility. Methods Alms1−/− (Foz/Foz) mice and wild-type littermates were fed normal chow (NC) or Western diet (WD) for up to 36 weeks (wk). Reversibility was modeled by switching WD-fed Foz/Foz mice at 12wk back to NC for 12wk. Cardiac assessment included echocardiography, invasive hemodynamics with dobutamine stimulation, histopathology, electron microscopy and isolated cardiomyocyte contractility. LV transcriptomes were profiled by bulk RNA sequencing and analyzed by differential expression and pathway enrichment. Results Foz/Foz mice on WD for 24wk developed metabolic syndrome and MASH with advanced liver fibrosis. Cardiac phenotyping showed LV hypertrophy, impaired cardiomyocyte contractility, reduced β-adrenergic reserve, elevated plasma BNP, and increased mortality while the ejection fraction was preserved (>50%), consistent with HFpEF. The progression of cardiac dysfunction was closely associated with liver fibrosis that developed during MASH. Switching WD-fed Foz/Foz mice at 12wk to normal chow diet reversed hepatic fibrosis, restored LV function, and reduced mortality, demonstrating plasticity of the liver-heart axis. LV transcriptomic analysis revealed that cardiac impairment in these mice was associated with mitochondrial dysfunction, altered substrate utilization, extracellular matrix remodeling, and metabolic stress; pathways that are similarly dysregulated in human HFpEF. Cardiac electron microscopy revealed swollen mitochondria with disrupted cristae, which improved following dietary intervention. Conclusions Mitochondrial dysfunction and fibroinflammatory remodeling are prominent features of MASLD-associated cardiac dysfunction. Reversal of hepatic and cardiac phenotypes with dietary intervention, together with elucidation of underlying pathways, establish the Foz/Foz model as a useful translational platform for studying liver-heart axis in MASLD.

Published in

A translational model of MASLD-associated HFpEF defines mitochondrial dysfunction and cardiac plasticity during disease progression and regression

Ganguly S, Gunes B, Gu Y et al. · Metabolism: clinical and experimental 2026 · PMID 42331139 · doi:10.1016/j.metabol.2026.156682

This dataset

Open GSE304630 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 GSE304630_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 PRJNA1301948 and SRA study SRP607107. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 42331139) ↗

Study design

6 conditions, mostly in triplicate

Foz_WD_24w ×3 WT_WD_24w ×3 Foz_Regression ×3 Foz_Chow_24w ×3 WT_Chow_24w ×3 Foz_WD_12w ×3

Supports a between-group comparison across 18 samples.

How we read this: 6 replicated groups read from 18 sample titles; they account for 18 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

GSM9154338 Foz_WD_24w_1 Foz_WD_24w
GSM9154339 Foz_WD_24w_2 Foz_WD_24w
GSM9154340 Foz_WD_24w_3 Foz_WD_24w
GSM9154341 WT_WD_24w_1 WT_WD_24w
GSM9154342 WT_WD_24w_2 WT_WD_24w
GSM9154343 WT_WD_24w_3 WT_WD_24w
GSM9154344 Foz_Regression_1 Foz_Regression
GSM9154345 Foz_Regression_2 Foz_Regression
GSM9154346 Foz_Regression_3 Foz_Regression
GSM9154347 Foz_Chow_24w_1 Foz_Chow_24w
GSM9154348 Foz_Chow_24w_2 Foz_Chow_24w
GSM9154349 Foz_Chow_24w_3 Foz_Chow_24w
GSM9154350 WT_Chow_24w_1 WT_Chow_24w
GSM9154351 WT_Chow_24w_2 WT_Chow_24w
GSM9154352 WT_Chow_24w_3 WT_Chow_24w
GSM9154353 Foz_WD_12w_1 Foz_WD_12w
GSM9154354 Foz_WD_12w_2 Foz_WD_12w
GSM9154355 Foz_WD_12w_3 Foz_WD_12w

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