GEO series

Hepatic insulin resistance promotes fructose-enriched diet-induced fatty liver diseases.

GSE270246 Mus musculus (mouse) RNA-seq (gene expression) 22 samples Submitted 2024/06/23 Platform GPL17021

At a glance

RNA-seq (gene expression) · mouse · 22 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: 22 samples: 11 conditions, mostly in duplicateGroups 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: Fructose and follistatin potentiate acute MASLD during complete hepatic insulin resistanceNature communications · 2025

Summary (written by the submitters)

Understanding mechanisms causing MAFLD (Metabolic Associated Fatty Liver Disease) and its progression to MASH (metabolic dysfunction-associated steatohepatitis) is clinically important and scientifically challenging. Hepatic insulin resistance is a common component in the progression of MAFLD in patients and experimental animals; however, hepatic steatosis caused by the HFD45% (high-fat diet) decreases during chronic hepatic IR generated by inactivation of Irs1/2 (LDKO), AKT1/2, or InsR 1-3—which is inconsistent with the expected relationship between IR and MAFLD in humans4.

Read the full summary ↓

Here we found that complete hepatic insulin resistance promotes the fructose-enriched GAN diet-induced MAFLD, including acute inflammation and MASH in LDKO mice. Unexpectedly, fructose phosphorylation catalyzed by hepatic Khk (ketohexokinase) was not required as acute MAFLD progressed strongly in LDKOKhkL/L mice fed the GAN diet. FoxO1 activated during hepatic IR induces Fst (Follistatin) expression and secretion from the liver of LDKO mice. Inactivation of hepatic FoxO1 in LTKO mice (LDKO•FoxO1L/L) or Fst in LDKOFstKO mice prevented acute MAFLD during the GAN diet. Consistently, overexpression of hepatic Fst promoted GAN diet-induced MAFLD/MASH and hepatic carcinoma. Mechanistically, circulating Fst promoted adipose tissue IR and lipolysis, which can deliver FFA (free fatty acid) to the liver for esterification with excess Gro3P (glycerol 3-phosphate) generated by fructose metabolism, although hepatic DNL (de novo lipogenesis) decreased strongly in LDKO mice while. Since circulating FST correlates positively with both T2D and MAFLD in humans, our results suggests that hepatic FST induced by progressive hepatic IR might promote MAFLD/MASH during the consumption of sugar-sweetened food and beverages consumed frequently by people and animals with T2D.

Published in

Fructose and follistatin potentiate acute MASLD during complete hepatic insulin resistance

Tao R, Stöhr O, Tok O et al. · Nature communications 2025 · PMID 41276502 · doi:10.1038/s41467-025-66296-5

This dataset

Open GSE270246 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 GSE270246_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 PRJNA1125865 and SRA study SRP514829. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41276502) ↗

Study design

11 conditions, mostly in duplicate

IRS1/2-HFD ×2 LDKO-HFD ×2 IRS1/2-Fruc ×2 LDKO-Fruc ×2 IRS1/2-GAN ×2 LDKO-GAN ×2 GFP-HFD ×2 FST315-HFD ×2 +3 more

Supports a between-group comparison across 22 samples.

How we read this: 11 replicated groups read from 22 sample titles; they account for 22 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

GSM8338073 IRS1/2-HFD-1 IRS1/2-HFD
GSM8338074 IRS1/2-HFD-2 IRS1/2-HFD
GSM8338075 LDKO-HFD-3 LDKO-HFD
GSM8338076 LDKO-HFD-4 LDKO-HFD
GSM8338077 IRS1/2-Fruc-5 IRS1/2-Fruc
GSM8338078 IRS1/2-Fruc-6 IRS1/2-Fruc
GSM8338079 LDKO-Fruc-7 LDKO-Fruc
GSM8338080 LDKO-Fruc-8 LDKO-Fruc
GSM8338081 IRS1/2-GAN-9 IRS1/2-GAN
GSM8338082 IRS1/2-GAN-10 IRS1/2-GAN
GSM8338083 LDKO-GAN-11 LDKO-GAN
GSM8338084 LDKO-GAN-12 LDKO-GAN
GSM8338085 GFP-HFD-13 GFP-HFD
GSM8338086 GFP-HFD-14 GFP-HFD
GSM8338087 FST315-HFD-15 FST315-HFD
GSM8338088 FST315-HFD-16 FST315-HFD
GSM8338089 CHOW-17 CHOW
GSM8338090 CHOW-18 CHOW
GSM8338091 GFP-GAN-19 GFP-GAN
GSM8338092 GFP-GAN-20 GFP-GAN
GSM8338093 FST315-GAN-21 FST315-GAN
GSM8338094 FST315-GAN-22 FST315-GAN

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