Evidence map›Paper›PMID 26017539›Full record

ArticlePloS one2015

Mouse models of diet-induced nonalcoholic steatohepatitis reproduce the heterogeneity of the human disease.

Mariana Verdelho Machado, Gregory Alexander Michelotti, Guanhua Xie, Thiago Almeida Pereira, Thiago Pereira de Almeida, Jerome Boursier, Brittany Bohnic, Cynthia D Guy, Anna Mae Diehl

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 220 papers.

0numbers the graph read from it
0cells of the map it votes in
220citing papers in PubMed
22.9field-weighted citation impact, top 1% 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

220 citing papers in PubMed, 376 citations in OpenAlex.

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160 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 1 institution in 2 countries.

Mariana Verdelho MachadoDivision of Gastroenterology, Department of Medicine, Duke University Medical Center, Durham, NC 27710, United States of America; Gastroenterology Department, Hospital de Santa Maria, CHLN, Lisbon, Portugal.
Gregory Alexander MichelottiDivision of Gastroenterology, Department of Medicine, Duke University Medical Center, Durham, NC 27710, United States of America.
Guanhua XieDivision of Gastroenterology, Department of Medicine, Duke University Medical Center, Durham, NC 27710, United States of America.
Thiago Almeida PereiraDivision of Gastroenterology, Department of Medicine, Duke University Medical Center, Durham, NC 27710, United States of America.
Thiago Pereira de Almeida
Jerome BoursierDivision of Gastroenterology, Department of Medicine, Duke University Medical Center, Durham, NC 27710, United States of America.
Brittany BohnicDivision of Endocrinology, Duke University Medical Center, Durham, NC 27710, United States of America.
Cynthia D GuyDivision of Pathology, Duke University Medical Center, Durham, NC 27710, United States of America.
Anna Mae DiehlDivision of Gastroenterology, Department of Medicine, Duke University Medical Center, Durham, NC 27710, United States of America.
Duke Medical Center · US

Funding

Hedgehog Signaling and Adult Liver RegenerationR01DK077794 · NIDDK · DUKE UNIVERSITY · PI DIEHL, ANNA MAE ELIZABETH · 2008 to 2020
$4.6M
LIVER DISEASE IN OBESITYR01DK053792 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI DIEHL, ANNA MAE ELIZABETH · 1999 to 2013
$3.6M
LIVER DISEASE IN OBESITYR55DK053792 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI DIEHL, ANNA MAE ELIZABETH · 1998 to 1998
–
NIDDK NIH HHS DK0077794NIDDK NIH HHS DK053792NIDDK NIH HHS R01 DK053792NIDDK NIH HHS R01 DK077794
6 · The paper itself

Abstract

BACKGROUND AND

aimsNon-alcoholic steatohepatitis (NASH), the potentially progressive form of nonalcoholic fatty liver disease (NAFLD), is the pandemic liver disease of our time. Although there are several animal models of NASH, consensus regarding the optimal model is lacking. We aimed to compare features of NASH in the two most widely-used mouse models: methionine-choline deficient (MCD) diet and Western diet.

methodsMice were fed standard chow, MCD diet for 8 weeks, or Western diet (45% energy from fat, predominantly saturated fat, with 0.2% cholesterol, plus drinking water supplemented with fructose and glucose) for 16 weeks. Liver pathology and metabolic profile were compared.

resultsThe metabolic profile associated with human NASH was better mimicked by Western diet. Although hepatic steatosis (i.e., triglyceride accumulation) was also more severe, liver non-esterified fatty acid content was lower than in the MCD diet group. NASH was also less severe and less reproducible in the Western diet model, as evidenced by less liver cell death/apoptosis, inflammation, ductular reaction, and fibrosis. Various mechanisms implicated in human NASH pathogenesis/progression were also less robust in the Western diet model, including oxidative stress, ER stress, autophagy deregulation, and hedgehog pathway activation.

conclusionFeeding mice a Western diet models metabolic perturbations that are common in humans with mild NASH, whereas administration of a MCD diet better models the pathobiological mechanisms that cause human NAFLD to progress to advanced NASH.

Indexed as

AnimalsApoptosisCholineCholine DeficiencyDietDisease Models, AnimalHumansLiverLiver CirrhosisMaleMetabolomeMethionineMiceMice, Inbred C57BLNon-alcoholic Fatty Liver DiseaseOxidative StressCholineMethionineTriglycerides

Identifiers

PMID26017539
PMCPMC4446215
OpenAlexW1575469908

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.