Evidence map›Paper›PMID 31295533›Full record

ArticleJournal of hepatology2019

The epigenetic regulator SIRT6 protects the liver from alcohol-induced tissue injury by reducing oxidative stress in mice.

Hyeong Geug Kim, Menghao Huang, Yue Xin, Yang Zhang, Xinge Zhang, Gaihong Wang, Sheng Liu, Jun Wan, Ali Reza Ahmadi, Zhaoli Sun and 3 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of hepatology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
75citing papers in PubMed, 1 pooled it
8.2field-weighted citation impact, top 2% 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

75 citing papers in PubMed, 1 synthesis or guideline pooled it, 127 citations in OpenAlex.

  1. Pooled it
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  5. [Histone deacetylases and alcohol-related liver disease].Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2026
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15 more citing papers are in PubMed but not listed here.

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

13 authors at 6 institutions in 2 countries.

Hyeong Geug KimDepartment of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Menghao HuangDepartment of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Yue XinSchool of Forensic Medicine, Xinxiang Medical University, Xinxiang, Henan 453003, PR China; Xinxiang Key Laboratory of Metabolism and Integrative Physiology, Xinxiang Medical University, Xinxiang, Henan 453003, PR China.
Yang ZhangDepartment of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Xinge ZhangSchool of Forensic Medicine, Xinxiang Medical University, Xinxiang, Henan 453003, PR China; Xinxiang Key Laboratory of Metabolism and Integrative Physiology, Xinxiang Medical University, Xinxiang, Henan 453003, PR China.
Gaihong WangDepartment of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Sheng LiuDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Jun WanDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Center of Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Ali Reza AhmadiDepartment of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Zhaoli SunDepartment of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Suthat LiangpunsakulDivision of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Roudebush Veterans Administration Medical Center, Indianapolis, IN 46202, USA.
Xiwen XiongSchool of Forensic Medicine, Xinxiang Medical University, Xinxiang, Henan 453003, PR China; Xinxiang Key Laboratory of Metabolism and Integrative Physiology, Xinxiang Medical University, Xinxiang, Henan 453003, PR China. Electronic address: xwxiong@xxmu.edu.cn.
Xiaocheng Charlie DongDepartment of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA. Electronic address: xcdong@iu.edu.
Indiana University – Purdue University Indianapolis · USIndiana University School of MedicineXinxiang Medical University · CNJohns Hopkins Medicine · USJohns Hopkins University · USRichard L. Roudebush VA Medical Center · US

Funding

Quality Assurance and Quality Control Project Management: Improving Submissions and Study Conduct in the Human Subjects Research Prior Approval ProcessUL1TR002529 · NCATS · INDIANA UNIVERSITY INDIANAPOLIS · PI MOE, SHARON M, WIEHE, SARAH ELIZABETH · 2018 to 2022
$27.2M
Translation CoreP30DK097512 · NIDDK · INDIANA UNIVERSITY INDIANAPOLIS · PI Carmella Evans-Molina · 2015 to 2026
$17.4M
Clinical Resources for Alcoholic Hepatitis InvestigationsR24AA025017 · NIAAA · JOHNS HOPKINS UNIVERSITY · PI ZHAOLI SUN · 2016 to 2026
$6.6M
Regulation of hepatic lipid metabolism by a novel Foxo pathwayR01DK091592 · NIDDK · INDIANA UNIVERSITY INDIANAPOLIS · PI DONG, X. CHARLIE · 2012 to 2016
$1.7M
Sestrin3 in the pathogenesis of alcoholic and non-alcoholic fatty liver diseaseR01DK107682 · NIDDK · INDIANA UNIVERSITY INDIANAPOLIS · PI DONG, X. CHARLIE, LIANGPUNSAKUL, SUTHAT · 2016 to 2019
$1.4M
Role of sirtuin 6 in the protection of liver from the alcohol-induced injuryR21AA024550 · NIAAA · INDIANA UNIVERSITY INDIANAPOLIS · PI DONG, X. CHARLIE · 2017 to 2018
$410k
Regulation of hepatic lipid metabolismR56DK091592 · NIDDK · INDIANA UNIVERSITY INDIANAPOLIS · PI DONG, X. CHARLIE · 2018 to 2018
$394k
NCATS NIH HHS UL1 TR002529NIAAA NIH HHS R21 AA024550NIAAA NIH HHS R24 AA025017NIDDK NIH HHS P30 DK097512NIDDK NIH HHS R01 DK091592NIDDK NIH HHS R01 DK107682NIDDK NIH HHS R56 DK091592
6 · The paper itself

Abstract

BACKGROUND &

aimsAs a nicotinamide adenine dinucleotide-dependent deacetylase and a key epigenetic regulator, sirtuin 6 (SIRT6) has been implicated in the regulation of metabolism, DNA repair, and inflammation. However, the role of SIRT6 in alcohol-related liver disease (ALD) remains unclear. The aim of this study was to investigate the function and mechanism of SIRT6 in ALD pathogenesis.

methodsWe developed and characterized Sirt6 knockout (KO) and transgenic mouse models that were treated with either control or ethanol diet. Hepatic steatosis, inflammation, and oxidative stress were analyzed using biochemical and histological methods. Gene regulation was analyzed by luciferase reporter and chromatin immunoprecipitation assays.

resultsThe Sirt6 KO mice developed severe liver injury characterized by a remarkable increase of oxidative stress and inflammation, whereas the Sirt6 transgenic mice were protected from ALD via normalization of hepatic lipids, inflammatory response, and oxidative stress. Our molecular analysis has identified a number of novel Sirt6-regulated genes that are involved in antioxidative stress, including metallothionein 1 and 2 (Mt1 and Mt2). Mt1/2 genes were downregulated in the livers of Sirt6 KO mice and patients with alcoholic hepatitis. Overexpression of Mt1 in the liver of Sirt6 KO mice improved ALD by reducing hepatic oxidative stress and inflammation. We also identified a critical link between SIRT6 and metal regulatory transcription factor 1 (Mtf1) via a physical interaction and functional coactivation. Mt1/2 promoter reporter assays showed a strong synergistic effect of SIRT6 on the transcriptional activity of Mtf1.

conclusionsOur data suggest that SIRT6 plays a critical protective role against ALD and it may serve as a potential therapeutic target for ALD. LAY SUMMARY: The liver, the primary organ for ethanol metabolism, can be damaged by the byproducts of ethanol metabolism, including reactive oxygen species. In this study, we have identified a key epigenetic regulator SIRT6 that plays a critical role in protecting the liver from oxidative stress-induced liver injury. Thus, our data suggest that SIRT6 may be a potential therapeutic target for alcohol-related liver disease.

Indexed as

AdultAnimalsDisease Models, AnimalDown-RegulationEpigenesis, GeneticEthanolFatty LiverFemaleGene Expression RegulationHepatocytesHumansLiverLiver Diseases, AlcoholicMaleMiceMice, KnockoutEthanolReactive Oxygen SpeciesSIRT6 protein, humanSirt6 protein, mouseSirtuinsAlcoholic hepatitisAlcohol-related liver diseaseCirrhosisEpigenetic regulationLiver injuryOxidative stressSIRT6Sirtuin

Identifiers

PMID31295533
PMCPMC6801027
OpenAlexW2958512921

What OpenQuestion holds

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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.