Evidence mapPaperPMID 41720949Full record

Articlenpj metabolic health and disease2026

Adipose tissue-derived MFG-E8 promotes hepatic inflammation and fibrosis through macrophage activation in a mouse MASH model.

Masashi Kuroda, Kazuhiro Nomura, Azumi Wada, Yui Hatano, Miki Ogawa, Saya Okamoto, Etsuko Ishikawa, Yuna Izumi-Mishima, Sonoko Yasui-Yamada, Yasuo M Tsutsumi and 3 more

Abstract read
In one paragraph

Article in npj metabolic health and disease, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

13 authors.

Masashi KurodaDepartment of Nutrition and Metabolism, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima City, Tokushima, Japan.
Kazuhiro NomuraDepartment of Nutrition and Metabolism, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima City, Tokushima, Japan.
Azumi WadaDepartment of Nutrition and Metabolism, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima City, Tokushima, Japan.
Yui HatanoDepartment of Nutrition and Metabolism, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima City, Tokushima, Japan.
Miki OgawaDepartment of Nutrition and Metabolism, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima City, Tokushima, Japan.
Saya OkamotoDepartment of Nutrition and Metabolism, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima City, Tokushima, Japan.
Etsuko IshikawaDepartment of Nutrition and Metabolism, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima City, Tokushima, Japan.
Yuna Izumi-MishimaDepartment of Nutrition and Metabolism, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima City, Tokushima, Japan.
Sonoko Yasui-YamadaDepartment of Nutrition and Metabolism, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima City, Tokushima, Japan.
Yasuo M TsutsumiDepartment of Anesthesiology and Critical Care, Hiroshima University, Hiroshima City, Hiroshima, Japan.
Nagakatsu HaradaDepartment of Health and Nutrition, Faculty of Nursing and Nutrition, The University of Shimane, Izumo City, Shimane, Japan.
Rie TsutsumiDepartment of Nutrition and Metabolism, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima City, Tokushima, Japan.
Hiroshi SakaueDepartment of Nutrition and Metabolism, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima City, Tokushima, Japan. hsakaue@tokushima-u.ac.jp.

Funding

KAKENHI grant 18K16205KAKENHI grant 23K24792KAKENHI grant 24K02859
6 · The paper itself

Abstract

Metabolic dysfunction-associated steatohepatitis (MASH) is characterized by hepatocellular injury, macrophage activation, and severe fibrosis, and often progresses to liver cirrhosis and hepatocellular carcinoma. Excessive accumulation of visceral fat exacerbates hepatic inflammation and fibrosis independently of fatty liver, but the underlying molecular mechanisms have remained unclear. We here identify MFG-E8 (milk fat globule-EGF8) as a secreted protein that is overexpressed in adipose tissue of obese mice and contributes to such exacerbation. MFG-E8 deficiency in MASH model (STAM-MASH) mice was associated with reduced hepatic expression of inflammation- and fibrosis-related genes without attenuation of steatosis. Conversely, MFG-E8 supplementation in MFG-E8 knockout mice intensified hepatic inflammation and promoted the formation of hepatic crownlike structures. Coculture of macrophages with apoptotic hepatocytes induced expression of inflammatory cytokine genes, and this effect was enhanced by the presence of exogenous MFG-E8 in the culture medium. Our findings suggest that adipose tissue-derived MFG-E8 infiltrates the liver and promotes macrophage-hepatocyte interaction, thereby contributing to hepatic inflammation and fibrosis in MASH.

Identifiers

PMID41720949
PMCPMC12923611

What Socratic holds

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LicenceCC BY
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Registered trials

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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.