Evidence map›Paper›PMID 40204101›Full record

ArticleGastroenterology2025

Adipose Tissue Macrophages in Metabolic Dysfunction-Associated Steatohepatitis Secrete Extracellular Vesicles That Activate Liver Fibrosis in Obese Male Mice.

Theresa V Rohm, Felipe Castellani Gomes Dos Reis, Karina Cunha E Rocha, Roi Isaac, Sean Strayer, Cairo Murphy, Gautam Bandyopadhyay, Hong Gao, Souradipta Ganguly, Tram Nguyen and 10 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Gastroenterology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing 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

17 citing papers in PubMed.

  1. Review
  2. Unifying and unique roles of non-coding RNA biomarkers in liver and heart fibrosis.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2026
    Review
  3. Review
  4. Review
  5. Review
  6. Review
  7. Review
  8. Review
  9. Article
  10. Review
  11. Review
  12. Review
  13. Article
  14. Review
  15. Review
  16. Review
  17. Review
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

20 authors.

Theresa V RohmDivision of Endocrinology and Metabolism, Department of Medicine, University of California San Diego, La Jolla, California. Electronic address: trohm@health.ucsd.edu.
Felipe Castellani Gomes Dos ReisDivision of Endocrinology and Metabolism, Department of Medicine, University of California San Diego, La Jolla, California.
Karina Cunha E RochaDivision of Endocrinology and Metabolism, Department of Medicine, University of California San Diego, La Jolla, California.
Roi IsaacDivision of Endocrinology and Metabolism, Department of Medicine, University of California San Diego, La Jolla, California.
Sean StrayerDivision of Endocrinology and Metabolism, Department of Medicine, University of California San Diego, La Jolla, California.
Cairo MurphyDivision of Endocrinology and Metabolism, Department of Medicine, University of California San Diego, La Jolla, California.
Gautam BandyopadhyayDivision of Endocrinology and Metabolism, Department of Medicine, University of California San Diego, La Jolla, California.
Hong GaoDivision of Endocrinology and Metabolism, Department of Medicine, University of California San Diego, La Jolla, California.
Souradipta GangulyDepartment of Medicine, School of Medicine, University of California San Diego, La Jolla, California; Center for Metabolic and Liver Diseases, Cancer Genome and Epigenetics Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California.
Tram NguyenDivision of Endocrinology and Metabolism, Department of Medicine, University of California San Diego, La Jolla, California.
Jinyue WangDivision of Endocrinology and Metabolism, Department of Medicine, University of California San Diego, La Jolla, California.
John E YouhannaDivision of Endocrinology and Metabolism, Department of Medicine, University of California San Diego, La Jolla, California.
David PackDivision of Endocrinology and Metabolism, Department of Medicine, University of California San Diego, La Jolla, California.
Xiao LiuDepartment of Surgery, University of California San Diego, School of Medicine, La Jolla, California.
Hyun Young KimDepartment of Medicine, School of Medicine, University of California San Diego, La Jolla, California; Department of Surgery, University of California San Diego, School of Medicine, La Jolla, California; College of Pharmacy, Dankook University, Cheonan, Chungnam, Republic of Korea.
Ishtiaq JeelaniDivision of Endocrinology and Metabolism, Department of Medicine, University of California San Diego, La Jolla, California.
Debanjan DharDepartment of Medicine, School of Medicine, University of California San Diego, La Jolla, California; Center for Metabolic and Liver Diseases, Cancer Genome and Epigenetics Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California.
Tatiana KisselevaDepartment of Surgery, University of California San Diego, School of Medicine, La Jolla, California.
Wei YingDivision of Endocrinology and Metabolism, Department of Medicine, University of California San Diego, La Jolla, California.
Jerrold M OlefskyDivision of Endocrinology and Metabolism, Department of Medicine, University of California San Diego, La Jolla, California. Electronic address: jolefsky@health.ucsd.edu.

Funding

The Southernearch Center for ALPD and CirrhosisP50AA011999 · NIAAA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI HIDEKAZU TSUKAMOTO · 1999 to 2026
$45.8M
Transgenic & Knock-out MouseP30DK063491 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ALAN R. SALTIEL · 2003 to 2026
$40.4M
San Diego Digestive Diseases Research CenterP30DK120515 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI LARS ECKMANN, Bernd G. Schnabl · 2019 to 2026
$10.8M
Transcriptional co-regulators and macrophage gene expressionR01DK091183 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GLASS, CHRISTOPHER K · 2011 to 2025
$9.9M
U of Calif, San Diego Neuroscience Microscopy ImagingP30NS047101 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GLEESON, JOSEPH G, ZHENG, BINHAI · 2003 to 2022
$9.0M
Inactivation of Hepatic Stellate Cells During Reversal of Liver FibrosisR01DK099205 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BRENNER, DAVID A., KISSELEVA, TATIANA · 2014 to 2025
$4.8M
The Role of Portal Fibroblasts in Cholestatic Liver FibrosisR01DK101737 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KISSELEVA, TATIANA · 2014 to 2025
$3.8M
Novel IL-23 inhibitor for the treatment of alcohol associated liver diseaseU01AA029019 · NIAAA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KISSELEVA, TATIANA, LOOMBA, ROHIT · 2020 to 2024
$3.7M
The role of IL-17 signaling in alcohol-induced HCCR01AA028550 · NIAAA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BRENNER, DAVID A., KISSELEVA, TATIANA · 2021 to 2025
$2.3M
Mechanisms by which hepatocyte extracellular miRNAs mediate peripheral insulin sensitivityR01DK125560 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI YING, WEI · 2021 to 2025
$2.0M
The Role of IL-17 in Alcoholic Liver Disease and CancerU01AA022614 · NIAAA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KARIN, MICHAEL, KISSELEVA, TATIANA · 2014 to 2018
$1.8M
Effects of Fractalkine on Beta Cell FunctionR01DK101395 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI OLEFSKY, JERROLD MICHAEL · 2014 to 2017
$1.6M
NIAAA NIH HHS P50 AA011999NIAAA NIH HHS R01 AA028550NIAAA NIH HHS U01 AA022614NIAAA NIH HHS U01 AA029019NICHD NIH HHS R21 HD107516NIDDK NIH HHS P30 DK063491NIDDK NIH HHS P30 DK120515NIDDK NIH HHS R00 DK115998NIDDK NIH HHS R01 DK091183NIDDK NIH HHS R01 DK099205NIDDK NIH HHS R01 DK101395NIDDK NIH HHS R01 DK101737NIDDK NIH HHS R01 DK125560NINDS NIH HHS P30 NS047101
6 · The paper itself

Abstract

BACKGROUND &

aimsGiven the need for effective interventions in metabolic dysfunction-associated steatohepatitis (MASH), understanding the role of adipose tissue macrophage (ATM)-derived small extracellular vesicles (sEVs) is important. We aimed to evaluate the contribution of MASH-ATM-sEVs to the development of liver fibrosis in obese male mice.

methodsUsing flow cytometry and nanoparticle tracking analysis, we characterized MASH-ATMs and their secreted sEVs. We assessed the fibrogenic effects of sEVs from MASH-ATMs or anti-inflammatory macrophages on stellate cells in vitro and in mice in vivo. In addition, we isolated Dicer knockdown microRNA (miRNA)-depleted sEVs from MASH-ATMs and cotreated stellate cells with MASH-ATM-sEVs and miR-155 or miR-34a antagomirs.

resultsMASH-ATMs exhibited a pro-inflammatory and lipid-associated phenotype, secreting sEVs enriched in the fibrogenic miRNAs, miR-155 and miR-34a, which also down-regulate Pparg. In vitro, MASH-ATM-sEVs induced hepatic stellate cell activation and fibrogenesis and exacerbated liver fibrosis when administered to obese mice. In addition, anti-inflammatory macrophage sEVs mitigated fibrosis both in vitro and in vivo. miRNA-free Dicer knockdown-MASH-ATM-sEVs were without effects and cotreatment with miR-155/miR-34a antagomirs blocked the effects of MASH-ATM-sEVs to induce hepatic stellate cell activation.

conclusionsThis study demonstrated the role of MASH-ATM-sEVs in promoting liver fibrosis in obesity. Identification of the fibrogenic miRs, miR-155, and miR-34a, within MASH-ATM-sEVs, highlights the mechanistic importance of extrahepatic signals in MASH. These findings showed the therapeutic potential of modulating macrophage phenotypes and their sEV cargo to ameliorate MASH.

Indexed as

Adipose TissueExtracellular VesiclesLiverLiver CirrhosisMacrophagesNon-alcoholic Fatty Liver DiseaseObesityAnimalsCells, CulturedDEAD-box RNA HelicasesDisease Models, AnimalHepatic Stellate CellsMaleMiceMice, Inbred C57BLMicroRNAsDEAD-box RNA HelicasesDicer1 protein, mouseMicroRNAsMirn155 microRNA, mouseMIRN34a microRNA, mouseRibonuclease IIIAdipose Tissue MacrophagesExosomesLipid-Associated MacrophagesMASHMicroRNA

Identifiers

PMID40204101
PMCPMC13197014

What Socratic holds

Textmetadata
LicenceTDM
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.