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Hepatic FoxO3 Supports Metabolic Resilience, Attenuates Age-Associated Obesity and Metabolic Dysfunction, and Mitigates Diet-Induced Steatohepatitis

GSE328603 Mus musculus (mouse) RNA-seq (gene expression) 12 samples Submitted 2026/07/29 Platform GPL34290
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: 3 × Liver, floxed control_Fasted vs 3 × Liver, hepatocyte-specific Foxo3 KO_Fasted vs 3 × Liver, floxed control_Fed vs 3 × Liver, hepatocyte-specific Foxo3 KO_FedGroups 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
Hepatic FoxO3 Supports Metabolic Resilience, Attenuates Age-Associated Obesity and Metabolic Dysfunction, and Mitigates Diet-Induced SteatohepatitisAging and disease · 2026
Summary (written by the submitters)
Forkhead box O3 (FoxO3) is implicated in aging and metabolic regulation; however, its roles in the local and systemic control of aging remain incompletely understood. In this study, we characterized the effects of hepatocyte-specific Foxo3 deletion on hepatic metabolic and whole-body energy homeostasis during aging, and the susceptibility of mice to metabolic disease.
Read the full summary ↓
Male hepatocyte-specific Foxo3 knockout (h-Foxo3-/-) mice developed moderate obesity and higher plasma insulin levels by middle age, despite no difference in food intake compared with wild-type mice. Indirect calorimetry revealed lower energy expenditure relative to body weight, a higher respiratory quotient, and less fatty acid oxidation, indicating a shift toward carbohydrate-dependent energy metabolism. Adipose tissue exhibited inflammatory cell infiltration and high expression of inflammatory and senescence markers, consistent with systemic insulin resistance. Although these findings suggested that hepatokine signaling regulates systemic metabolism, there was limited direct evidence for FoxO3-dependent hepatokine secretion. RNA-sequencing analysis suggested that fatty acid processing and xenobiotic and detoxification pathways were suppressed in h-Foxo3-/- liver and that gluconeogenic and proinflammatory programs were activated. h-Foxo3-/- mice exhibited hepatic steatosis and an increase in the oxidized glutathione concentration when consuming a regular diet, and those consuming a fat-, fructose-, and cholesterol-rich diet, which induces steatohepatitis, showed more severe fibrosis than controls. Collectively, these findings suggest that hepatic FoxO3 is a key regulator coordinating hepatic lipid processing, xenobiotic metabolism and detoxification, susceptibility to metabolic disorders, and systemic metabolic flexibility. Thus, hepatic FoxO3 contributes to the maintenance of metabolic resilience during aging.
Published in
Hepatic FoxO3 Supports Metabolic Resilience, Attenuates Age-Associated Obesity and Metabolic Dysfunction, and Mitigates Diet-Induced Steatohepatitis
Komatsu T, Park S, Kim S et al. · Aging and disease 2026 · PMID 42508387 · doi:10.14336/AD.2026.0477
This dataset
Open GSE328603 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 GSE328603_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 PRJNA1455965 and SRA study SRP693512. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 42508387) ↗
Study design
3 × Liver, floxed control_Fasted vs 3 × Liver, hepatocyte-specific Foxo3 KO_Fasted vs 3 × Liver, floxed control_Fed vs 3 × Liver, hepatocyte-specific Foxo3 KO_Fed

Supports a between-group comparison across 12 samples.

How we read this: 4 replicated groups read from 12 sample titles; they account for 12 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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