Evidence map›Paper›PMID 37134024›Full record

ArticlePloS one2023

Concomitant western diet and chronic-binge alcohol dysregulate hepatic metabolism.

Delfin Gerard Buyco, Joseph L Dempsey, Eleonora Scorletti, Sookyoung Jeon, Chelsea Lin, Julia Harkin, Susovon Bayen, Emma E Furth, Jasmin Martin, Monique Delima and 5 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed, 1 pooled it
3.4field-weighted citation impact, top 7% 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

13 citing papers in PubMed, 1 synthesis or guideline pooled it, 16 citations in OpenAlex.

  1. Pooled it
  2. Therapeutics for Alcohol-Associated Liver Disease.Annual review of pharmacology and toxicology · 2026
    Review
  3. Article
  4. Review
  5. Article
  6. Review
  7. Article
  8. Review
  9. Article
  10. Interaction between fatty acid oxidation and ethanol metabolism in liver.American journal of physiology. Gastrointestinal and liver physiology · 2024
    Review
  11. Alcohol-associated liver disease.The Journal of clinical investigation · 2024
    Review
  12. Article
  13. 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

15 authors at 3 institutions in 2 countries.

Delfin Gerard BuycoDivision of Gastroenterology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
Joseph L DempseyDivision of Gastroenterology, Department of Medicine, School of Medicine, University of Washington, Seattle, Washington, United States of America.
Eleonora ScorlettiDivision of Gastroenterology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
Sookyoung JeonDivision of Gastroenterology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.ORCID 0000-0002-3620-0851
Chelsea LinDivision of Gastroenterology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.ORCID 0000-0003-3696-121X
Julia HarkinDivision of Gastroenterology, Department of Medicine, School of Medicine, University of Washington, Seattle, Washington, United States of America.
Susovon BayenDivision of Gastroenterology, Department of Medicine, School of Medicine, University of Washington, Seattle, Washington, United States of America.
Emma E FurthDepartment of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
Jasmin MartinDivision of Gastroenterology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.ORCID 0000-0002-6581-2005
Monique DelimaDivision of Gastroenterology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
Royce HooksDivision of Gastroenterology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
Jaimarie Sostre-ColónInstitute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
Sina A GharibDivision of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, University of Washington, Seattle, Washington, United States of America.ORCID 0000-0002-2480-4367
Paul M TitchenellInstitute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
Rotonya M CarrDivision of Gastroenterology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
University of Pennsylvania · USUniversity of Washington · USHallym University · KR

Funding

VIRAL VECTOR COREP30DK019525 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI MITCHELL A. LAZAR · 1986 to 2026
$48.3M
Vector and Transgenic Mouse CoreP30DK017047 · NIDDK · UNIVERSITY OF WASHINGTON · PI Sakeneh Zraika · 1986 to 2026
$41.4M
TRANSGENIC AND CHIMERIC MOUSE COREP30DK050306 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI Ken Hashigiwa Cadwell · 1997 to 2026
$32.5M
UNIVERSITY OF WASHINGTON GI TRAINING GRANTT32DK007742 · NIDDK · UNIVERSITY OF WASHINGTON · PI GRADY, WILLIAM MALLORY · 1996 to 2022
$4.7M
Molecular Mechanisms Of Post-Transplant Recurrent Alcoholic Liver DiseaseR01AA026302 · NIAAA · UNIVERSITY OF WASHINGTON · PI ROTONYA M CARR · 2017 to 2026
$3.2M
Hepatic mTORC1 Signaling and the Regulation of Lipid HomeostasisR01DK125497 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI TITCHENELL, PAUL MICHAEL · 2021 to 2024
$1.7M
NIAAA NIH HHS R01 AA026302NIDDK NIH HHS P30 DK017047NIDDK NIH HHS P30 DK019525NIDDK NIH HHS P30 DK050306NIDDK NIH HHS R01 DK125497NIDDK NIH HHS T32 DK007742
6 · The paper itself

Abstract

BACKGROUND AND

aimsThere is significant overlap between non-alcoholic fatty liver disease (NAFLD) and alcohol-associated liver disease (ALD) with regards to risk factors and disease progression. However, the mechanism by which fatty liver disease arises from concomitant obesity and overconsumption of alcohol (syndrome of metabolic and alcohol-associated fatty liver disease; SMAFLD), is not fully understood.

methodsMale C57BL6/J mice were fed chow diet (Chow) or high-fructose, high-fat, high-cholesterol diet (FFC) for 4 weeks, then administered either saline or ethanol (EtOH, 5% in drinking water) for another 12 weeks. The EtOH treatment also consisted of a weekly 2.5 g EtOH/kg body weight gavage. Markers for lipid regulation, oxidative stress, inflammation, and fibrosis were measured by RT-qPCR, RNA-seq, Western blot, and metabolomics.

resultsCombined FFC-EtOH induced more body weight gain, glucose intolerance, steatosis, and hepatomegaly compared to Chow, EtOH, or FFC. Glucose intolerance by FFC-EtOH was associated with decreased hepatic protein kinase B (AKT) protein expression and increased gluconeogenic gene expression. FFC-EtOH increased hepatic triglyceride and ceramide levels, plasma leptin levels, hepatic Perilipin 2 protein expression, and decreased lipolytic gene expression. FFC and FFC-EtOH also increased AMP-activated protein kinase (AMPK) activation. Finally, FFC-EtOH enriched the hepatic transcriptome for genes involved in immune response and lipid metabolism.

conclusionsIn our model of early SMAFLD, we observed that the combination of an obesogenic diet and alcohol caused more weight gain, promoted glucose intolerance, and contributed to steatosis by dysregulating leptin/AMPK signaling. Our model demonstrates that the combination of an obesogenic diet with a chronic-binge pattern alcohol intake is worse than either insult alone.

Indexed as

Glucose IntoleranceLiver Diseases, AlcoholicNon-alcoholic Fatty Liver DiseaseAMP-Activated Protein KinasesAnimalsDiet, High-FatDiet, WesternEthanolLeptinLipid MetabolismLiverMaleMiceMice, Inbred C57BLObesityAMP-Activated Protein KinasesEthanolLeptin

Identifiers

PMID37134024
PMCPMC10155975
OpenAlexW4367833898

What OpenQuestion holds

Textmetadata
LicenceCC0
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 OpenQuestion graph.