Evidence map›Paper›PMID 37859621›Full record

SynthesisEMBO molecular medicine2023

Multi-omic network analysis identified betacellulin as a novel target of omega-3 fatty acid attenuation of western diet-induced nonalcoholic steatohepatitis.

Jyothi Padiadpu, Manuel Garcia-Jaramillo, Nolan K Newman, Jacob W Pederson, Richard Rodrigues, Zhipeng Li, Sehajvir Singh, Philip Monnier, Giorgio Trinchieri, Kevin Brown and 4 more

Open access · goldAbstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in EMBO molecular medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed, 1 pooled it
2.1field-weighted citation impact, top 11% 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

10 citing papers in PubMed, 1 synthesis or guideline pooled it, 10 citations in OpenAlex.

  1. Pooled it
  2. Review
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  4. Review
  5. Review
  6. Article
  7. Article
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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

14 authors at 2 institutions in 1 country.

Jyothi PadiadpuCollege of Pharmacy, Oregon State University, Corvallis, OR, USA.ORCID 0000-0002-9507-6133
Manuel Garcia-Jaramillo *Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR, USA.ORCID 0000-0003-2987-2913
Nolan K Newman *College of Pharmacy, Oregon State University, Corvallis, OR, USA.
Jacob W Pederson *Carlson College of Veterinary Medicine, Oregon State University, Corvallis, OR, USA.
Richard RodriguesCollege of Pharmacy, Oregon State University, Corvallis, OR, USA.
Zhipeng LiCarlson College of Veterinary Medicine, Oregon State University, Corvallis, OR, USA.
Sehajvir SinghCollege of Pharmacy, Oregon State University, Corvallis, OR, USA.ORCID 0009-0004-0751-6541
Philip MonnierCollege of Pharmacy, Oregon State University, Corvallis, OR, USA.
Giorgio TrinchieriCancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Kevin BrownCollege of Pharmacy, Oregon State University, Corvallis, OR, USA.
Amiran K DzutsevCancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0003-0749-4149
Natalia ShulzhenkoCarlson College of Veterinary Medicine, Oregon State University, Corvallis, OR, USA.ORCID 0000-0003-0077-8456
Donald B JumpNutrition Program, School of Biological and Population Health Sciences, Linus Pauling Institute, Oregon State University, Corvallis, OR, USA.ORCID 0000-0002-9473-6283
Andrey MorgunCollege of Pharmacy, Oregon State University, Corvallis, OR, USA.ORCID 0000-0002-8924-6108
Oregon State University · USNational Institutes of Health · US

Funding

NIDDK NIH HHS R01 DK094600NIDDK NIH HHS R01 DK103761NIDDK NIH HHS R01 DK112360
6 · The paper itself

Abstract

Clinical and preclinical studies established that supplementing diets with ω3 polyunsaturated fatty acids (PUFA) can reduce hepatic dysfunction in nonalcoholic steatohepatitis (NASH) but molecular underpinnings of this action were elusive. Herein, we used multi-omic network analysis that unveiled critical molecular pathways involved in ω3 PUFA effects in a preclinical mouse model of western diet induced NASH. Since NASH is a precursor of liver cancer, we also performed meta-analysis of human liver cancer transcriptomes that uncovered betacellulin as a key EGFR-binding protein upregulated in liver cancer and downregulated by ω3 PUFAs in animals and humans with NASH. We then confirmed that betacellulin acts by promoting proliferation of quiescent hepatic stellate cells, inducing transforming growth factor-β2 and increasing collagen production. When used in combination with TLR2/4 agonists, betacellulin upregulated integrins in macrophages thereby potentiating inflammation and fibrosis. Taken together, our results suggest that suppression of betacellulin is one of the key mechanisms associated with anti-inflammatory and anti-fibrotic effects of ω3 PUFA on NASH.

Indexed as

Fatty Acids, Omega-3Liver NeoplasmsNon-alcoholic Fatty Liver DiseaseAnimalsBetacellulinDiet, WesternDisease Models, AnimalFibrosisHumansLiverMiceMice, Inbred C57BLMultiomicsBetacellulinFatty Acids, Omega-3betacellulindocosahexaenoic acidmulti-omic networknonalcoholic steatohepatitisω3 PUFA

Identifiers

PMID37859621
PMCPMC10630881
OpenAlexW4387799269

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.