Evidence map›Paper›PMID 37914694›Full record

ArticleNature communications2023

Hepatocyte FBXW7-dependent activity of nutrient-sensing nuclear receptors controls systemic energy homeostasis and NASH progression in male mice.

Hui Xia, Catherine R Dufour, Younes Medkour, Charlotte Scholtes, Yonghong Chen, Christina Guluzian, Wafa B'chir, Vincent Giguère

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
3.6field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 17 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

Hui XiaGoodman Cancer Institute, McGill University, Montréal, QC, H3A 1A3, Canada.ORCID 0000-0002-3603-1920
Catherine R DufourGoodman Cancer Institute, McGill University, Montréal, QC, H3A 1A3, Canada.ORCID 0000-0001-7324-3458
Younes MedkourGoodman Cancer Institute, McGill University, Montréal, QC, H3A 1A3, Canada.ORCID 0000-0003-2913-2384
Charlotte ScholtesGoodman Cancer Institute, McGill University, Montréal, QC, H3A 1A3, Canada.ORCID 0000-0002-4982-5308
Yonghong ChenGoodman Cancer Institute, McGill University, Montréal, QC, H3A 1A3, Canada.
Christina GuluzianGoodman Cancer Institute, McGill University, Montréal, QC, H3A 1A3, Canada.
Wafa B'chirGoodman Cancer Institute, McGill University, Montréal, QC, H3A 1A3, Canada.
Vincent GiguèreGoodman Cancer Institute, McGill University, Montréal, QC, H3A 1A3, Canada. vincent.giguere@mcgill.ca.ORCID 0000-0001-9567-3694
McGill University · CAMcGill University Health Centre · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Nonalcoholic steatohepatitis (NASH) is epidemiologically associated with obesity and diabetes and can lead to liver cirrhosis and hepatocellular carcinoma if left untreated. The intricate signaling pathways that orchestrate hepatocyte energy metabolism and cellular stress, intrahepatic cell crosstalk, as well as interplay between peripheral tissues remain elusive and are crucial for the development of anti-NASH therapies. Herein, we reveal E3 ligase FBXW7 as a key factor regulating hepatic catabolism, stress responses, systemic energy homeostasis, and NASH pathogenesis with attenuated FBXW7 expression as a feature of advanced NASH. Multiomics and pharmacological intervention showed that FBXW7 loss-of-function in hepatocytes disrupts a metabolic transcriptional axis conjointly controlled by the nutrient-sensing nuclear receptors ERRα and PPARα, resulting in suppression of fatty acid oxidation, elevated ER stress, apoptosis, immune infiltration, fibrogenesis, and ultimately NASH progression in male mice. These results provide the foundation for developing alternative strategies co-targeting ERRα and PPARα for the treatment of NASH.

Indexed as

Liver NeoplasmsNon-alcoholic Fatty Liver DiseaseAnimalsF-Box-WD Repeat-Containing Protein 7HepatocytesHomeostasisLiverMaleMiceMice, Inbred C57BLNutrientsPPAR alphaReceptors, Cytoplasmic and NuclearF-Box-WD Repeat-Containing Protein 7Fbxw7 protein, mouseNutrientsPPAR alphaReceptors, Cytoplasmic and Nuclear

Identifiers

PMID37914694
PMCPMC10620240
OpenAlexW4388127808

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.