GEO series

Intestinal lipase inhibition uncouples diet-induced obesity from MASH by remodeling the hepatic lipidome

GSE333221 Mus musculus (mouse) RNA-seq (gene expression) 12 samples Submitted 2026/07/27 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: 6 × Liver_Orlistat vs 6 × Liver_ControlGroups 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)

Dietary fatty acids exert distinct effects on hepatic metabolism. Intestinal lipase inhibition, used clinically for obesity, promotes weight loss by indiscriminately reducing dietary fat absorption, yet its impact on hepatic lipid metabolism in metabolic dysfunction-associated steatohepatitis (MASH) remains poorly defined. Here, we examined the metabolic consequences of lipase inhibition of fat absorption in MASH.

Read the full summary ↓

To induce MASH, C57BL/6J mice were fed the high-fat Gubra-Amylin NASH (GAN) diet with or without the lipase inhibitor orlistat for 32 weeks. Orlistat protected against diet-induced obesity by promoting fat malabsorption but failed to prevent the progression of hepatomegaly, steatosis, and fibrosis across longitudinal ultrasound imaging, biochemical assessments, and endpoint histology. Despite limiting weight gain, orlistat unexpectedly exacerbated hepatic inflammation. Lipidomic analyses revealed that indiscriminate inhibition of fat absorption depleted the liver of essential polyunsaturated fatty acids while increasing saturated fatty acids. This shift was associated with increased hepatic lipogenesis and proinflammatory signaling, preventing protection from MASH. In summary, lipase inhibition of intestinal fat absorption uncouples obesity from liver disease progression by reshaping the hepatic lipidome. These findings underscore the importance of dietary fat and hepatic lipid composition as key drivers of MASH pathogenesis.

This dataset

Open GSE333221 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 GSE333221_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 PRJNA1470520 and SRA study SRP703666. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗

Study design

6 × Liver_Orlistat vs 6 × Liver_Control

Supports a between-group comparison across 12 samples.

How we read this: 2 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

GSM9759292 Liver_Orlistat_2 Liver_Orlistat
GSM9759293 Liver_Orlistat_3 Liver_Orlistat
GSM9759294 Liver_Orlistat_4 Liver_Orlistat
GSM9759295 Liver_Control_14 Liver_Control
GSM9759296 Liver_Control_15 Liver_Control
GSM9759297 Liver_Control_16 Liver_Control
GSM9759298 Liver_Orlistat_41 Liver_Orlistat
GSM9759299 Liver_Orlistat_42 Liver_Orlistat
GSM9759300 Liver_Orlistat_43 Liver_Orlistat
GSM9759301 Liver_Control_49 Liver_Control
GSM9759302 Liver_Control_50 Liver_Control
GSM9759303 Liver_Control_52 Liver_Control

Datasets on a similar topic

GSE282601 Intestinal epithelial cell EphB4 deficiency on high fat diet-induced obesity 16 samples shares diet-induced, intestinal, obesity
GSE302447 A multi-functional oral small molecule targeting energy and lipid metabolism as a treatment for diet-induced obesity 67 samples shares diet-induced, obesity
GSE295974 Single-cell multi-omics reveal coordinated neoplastic and immune remodeling following KRAS inhibition 64 samples shares inhibition, remodeling
GSE262523 Diet-Induced Obesity Disrupts Sexually Dimorphic Gene Expression in Liver and Adipose Tissue in Mice 48 samples shares diet-induced, obesity
GSE292815 Diet-induced phospholipid remodeling dictates ferroptosis sensitivity and tumorigenesis in the pancreas 39 samples shares diet-induced, remodeling
GSE252343 Hofbauer cells and fetal brain microglia share transcriptional profiles and responses to maternal diet-induced obesity 34 samples shares diet-induced, obesity
GSE315007 Sex- and hepatocyte Pparg-dependent hepatic effects of a high fat diet containing 60% kcal from fat and 2% cholesterol, which was supplemented with 10% fructose in the drinking water (HFC+Fr) to induce diet-induced obesity in male and female mice. 30 samples shares diet-induced, obesity
GSE269053 Two-hit mouse model of heart failure with preserved ejection fraction combining diet-induced obesity and renin-mediated hypertension 21 samples shares diet-induced, obesity

Search all mouse RNA-seq datasets in GEO →

Share this dataset

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.