Evidence mapPaperPMID 33177546Full record

ArticleScientific reports2020

PPARα agonist and metformin co-treatment ameliorates NASH in mice induced by a choline-deficient, amino acid-defined diet with 45% fat.

Shinya Okishio, Kanji Yamaguchi, Hiroshi Ishiba, Nozomi Tochiki, Kota Yano, Aya Takahashi, Seita Kataoka, Keiichiroh Okuda, Yuya Seko, Yu Liu and 9 more

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.0field-weighted citation impact, top 22% 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, 16 citations in OpenAlex.

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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

19 authors at 3 institutions in 1 country.

Shinya OkishioMolecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyou-ku, Kyoto, 602-8566, Japan.
Kanji YamaguchiMolecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyou-ku, Kyoto, 602-8566, Japan. ykanji@koto.kpu-m.ac.jp.
Hiroshi IshibaMolecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyou-ku, Kyoto, 602-8566, Japan.
Nozomi TochikiMolecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyou-ku, Kyoto, 602-8566, Japan.
Kota YanoMolecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyou-ku, Kyoto, 602-8566, Japan.
Aya TakahashiMolecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyou-ku, Kyoto, 602-8566, Japan.
Seita KataokaMolecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyou-ku, Kyoto, 602-8566, Japan.
Keiichiroh OkudaMolecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyou-ku, Kyoto, 602-8566, Japan.
Yuya SekoMolecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyou-ku, Kyoto, 602-8566, Japan.
Yu LiuMolecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyou-ku, Kyoto, 602-8566, Japan.
Hideki FujiiMolecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyou-ku, Kyoto, 602-8566, Japan.
Daiki TakahashiPharmaceutical Research Department, Biological Research Laboratories, Nissan Chemical Corporation, Saitama, Japan.
Yusuke ItoPharmaceutical Research Department, Biological Research Laboratories, Nissan Chemical Corporation, Saitama, Japan.
Junji KamonPharmaceutical Research Department, Biological Research Laboratories, Nissan Chemical Corporation, Saitama, Japan.
Atsushi UmemuraMolecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyou-ku, Kyoto, 602-8566, Japan.
Michihisa MoriguchiMolecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyou-ku, Kyoto, 602-8566, Japan.
Kohichiroh YasuiMolecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyou-ku, Kyoto, 602-8566, Japan.
Takeshi OkanoueDepartment of Gastroenterology and Hepatology, Saiseikai Suita Hospital, Osaka, Japan.
Yoshito ItohMolecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyou-ku, Kyoto, 602-8566, Japan.
Kyoto Prefectural University of Medicine · JPNissan Chemical Corporation (Japan) · JPSaiseikai Suita Hospital · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

We explored the beneficial effects of GW7647, a peroxisome proliferator activated receptor α (PPARα) agonist, and metformin, an anti-diabetic drug on an advanced nonalcoholic steatohepatitis (NASH) model in rodents and investigated the possible mechanisms involved. Mice were fed control chow or a choline-deficient L-amino acid-defined diet containing 45% fat (HF-CDAA). The mice fed HF-CDAA diets for 16 weeks were divided into four groups: the no treatment (HF-CDAA), HF-CDAA containing 1000 mg/kg metformin, HF-CDAA containing 10 mg/kg GW7647, and HF-CDAA with both metformin and GW7647 groups. Metformin alone slightly deteriorated the aspartate and alanine aminotransferase (AST/ALT) values, whereas co-treatment with GW7647 and metformin greatly suppressed liver injury and fibrosis via activation of the AMP-activated protein kinase (AMPK) pathway. Further study revealed that co-treatment decreased the expression of inflammatory-, fibrogenesis-, and endoplasmic reticulum (ER) stress-related genes and increased the oxidized nicotinamide adenine dinucleotide (NAD)/reduced nicotinamide adenine dinucleotide (NADH) ratio, suggesting the superiority of co-treatment due to restoration of mitochondrial function. The additive benefits of a PPARα agonist and metformin in a HF-CDAA diet-induced advanced NASH model was firstly demonstrated, possibly through restoration of mitochondrial function and AMPK activation, which finally resulted in suppression of hepatic inflammation, ER stress, then, fibrosis.

Indexed as

Alanine TransaminaseAmino AcidsAnimalsAnti-Inflammatory Agents, Non-SteroidalAntioxidantsAspartate AminotransferasesButyratesCholine DeficiencyDietDisease Models, AnimalDrug Therapy, CombinationEndoplasmic Reticulum StressFibroblast Growth FactorsMaleMetforminMice, Inbred C57BLAlanine TransaminaseAmino AcidsAnti-Inflammatory Agents, Non-SteroidalAntioxidantsAspartate AminotransferasesButyratesfibroblast growth factor 21Fibroblast Growth FactorsGW 7647MetforminPhenylurea CompoundsPPAR alphaPpara protein, mouse

Identifiers

PMID33177546
PMCPMC7658250
OpenAlexW3104139858

What Socratic holds

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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.