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Hepatic CB1 receptor signaling triggers Gi/oα-mediated lipolysis in lean mice but Gsα-mediated lipogenesis in obese mice

GSE304736 Mus musculus (mouse) RNA-seq (gene expression) 23 samples Submitted 2025/08/06 Platform GPL21103
At a glance

RNA-seq (gene expression) · mouse · 23 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
23 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
Hepatic CB1 receptor signaling triggers G(i/o)α-mediated lipolysis in lean mice but G(s)α-mediated lipogenesis in obese miceMetabolism: clinical and experimental · 2025
Summary (written by the submitters)
Objectives: Obesity-induced steatotic liver disease (SLD) is driven by the uptake of adipocyte-derived fatty acids (FAs) into hepatocytes via the FA translocase CD36, which also prevents their consumption by inhibiting AMP kinase (AMPK)-mediated FA oxidation (FAO). We explored the role of hepatocyte CB1 receptors (hCB1R) in controlling hepatic triglyceride (TG) content by regulating CD36 and its downstream targets.
Read the full summary ↓
Methods: hCB1R knockout (hCB1Rko) mice and their control littermates kept on standard or high-fat diet were used to analyze hCB1R-mediated hepatic gene expression profile and lipid metabolism in intact mice and in cultured hepatocytes. Results: Multi-omics data indicate that hCB1R target a distinct set of genes associated with SLD, including Cd36. In mice with diet-induced obesity, hCB1R signaling via CD36-AMPK-FAO pathway contributes to both the development of SLD and its reversal by CB1R blockade. But, in lean mice hCB1R signaling inhibits CD36 expression and activates AMPK-mediated FAO. These opposite effects were replicated in AML12 mouse hepatocytes incubated with or without oleic acid (OA). OA, an endogenous ligand of GPR3, induced a switch in hCB1R signaling from a Gi/oα-mediated reduction in cAMP to a Gsα-mediated increase in cAMP in a GPR3/Gsα -dependent manner, facilitated by increasing the ratio of Gsα:Gi/oα proteins in the steatotic compared to lean liver. Conclusions: In the lean state, endocannabinoid activation of hCB1R increases FAO, which mitigates SLD, as reported for chronic marihuana smokers, whereas in obese mice hCB1R tonically inhibit FAO, which promotes SLD and underlies the anti-steatotic effect of peripheral CB1R blockade.
Published in
Hepatic CB1 receptor signaling triggers G(i/o)α-mediated lipolysis in lean mice but G(s)α-mediated lipogenesis in obese mice
Liu J, Oliverio A, Godlewski G et al. · Metabolism: clinical and experimental 2025 · PMID 40446956 · doi:10.1016/j.metabol.2025.156308
This dataset
Open GSE304736 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 GSE304736_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 PRJNA1302424 and SRA study SRP607157. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40446956) ↗
Study design
6 conditions, mostly in triplicate
LCB1-JD ×6 LM-V ×5 LCB1-RC ×3 LCB1-V ×3 LM-JD ×3 LM-RC ×3

Supports a between-group comparison across 23 samples.

How we read this: 6 replicated groups read from 23 sample titles; they account for 23 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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