Evidence map›Paper›PMID 27858497›Full record

ArticleEpigenetics2017

High fat diet and exercise lead to a disrupted and pathogenic DNA methylome in mouse liver.

Dan Zhou, Ryan A Hlady, Marissa J Schafer, Thomas A White, Chen Liu, Jeong-Hyeon Choi, Jordan D Miller, Lewis R Roberts, Nathan K LeBrasseur, Keith D Robertson

Erratum issuedOpen access · bronzeAbstract read
In one paragraph

Article in Epigenetics, 2017. 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 35 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed, 1 pooled it
3.0field-weighted citation impact, top 9% 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

35 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.

  1. Pooled it
  2. Crosstalk BetweenCancers · 2026
    Review
  3. Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Review
  10. Sweating it out: How physical activity can combat high genetic risk for nonalcoholic fatty liver disease.Liver international : official journal of the International Association for the Study of the Liver · 2023
    Article
  11. [Factors influencing the clinical phenotype of hepatolenticular degeneration].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2023
    Review
  12. Review
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  15. Review
  16. Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 5 institutions in 2 countries.

Dan Zhoua Department of Molecular Pharmacology and Experimental Therapeutics , Mayo Clinic , Rochester , MN , USA.
Ryan A Hladya Department of Molecular Pharmacology and Experimental Therapeutics , Mayo Clinic , Rochester , MN , USA.
Marissa J Schaferb Robert and Arlene Kogod Center on Aging, Mayo Clinic , Rochester , MN , USA.
Thomas A Whiteb Robert and Arlene Kogod Center on Aging, Mayo Clinic , Rochester , MN , USA.
Chen Liud Department of Pathology and Laboratory Medicine , Rutgers University , NJ , USA.
Jeong-Hyeon Choie Department of Applied Research , Marine Biodiversity Institute of Korea , Korea.
Jordan D Millerb Robert and Arlene Kogod Center on Aging, Mayo Clinic , Rochester , MN , USA.
Lewis R Robertsg Mayo Clinic Cancer Center , Mayo Clinic , Rochester , MN , USA.
Nathan K LeBrasseurb Robert and Arlene Kogod Center on Aging, Mayo Clinic , Rochester , MN , USA.
Keith D Robertsona Department of Molecular Pharmacology and Experimental Therapeutics , Mayo Clinic , Rochester , MN , USA.
Mayo Clinic in Arizona · USMayo Clinic in Florida · USMayo Clinic · USMarine Biodiversity Institute of Korea · KRRutgers, The State University of New Jersey · US

Funding

Women's Cancer ProgramP30CA015083 · NCI · MAYO CLINIC ROCHESTER · PI Felicity Enders · 1985 to 2026
$151.3M
PILOT AND FEASIBILTY PROGRAMP30DK084567 · NIDDK · MAYO CLINIC ROCHESTER · PI GREGORY J. GORES · 2009 to 2026
$22.2M
Systems Biology and Bioinformatics CoreP01AG041122 · NIA · MAYO CLINIC ROCHESTER · PI CAMPISI, JUDITH · 2012 to 2016
$9.8M
De novo methyltransferase function in chromatin &cancerR01CA114229 · NCI · UNIVERSITY OF FLORIDA · PI ROBERTSON, KEITH D · 2005 to 2017
$3.3M
Developmental pathways, environmental agents, and epigenetics in liver diseaseR01AA019976 · NIAAA · MAYO CLINIC ROCHESTER · PI LIU, CHEN, ROBERTSON, KEITH D · 2011 to 2015
$3.0M
Aging and Resiliency in Mice: Optimizing Assessment Protocols and Testing InterventionsR01AG053832 · NIA · MAYO CLINIC ROCHESTER · PI LEBRASSEUR, NATHAN K, MILLER, JORDAN D · 2016 to 2020
$2.0M
Role of SIRT6 in calcific aortic valve diseaseR01HL111121 · NHLBI · MAYO CLINIC ROCHESTER · PI MILLER, JORDAN D · 2013 to 2017
$2.0M
NHLBI NIH HHS R01 HL111121NIA NIH HHS P01 AG041122NIA NIH HHS R01 AG053832
6 · The paper itself

Abstract

High-fat diet consumption and sedentary lifestyle elevates risk for obesity, non-alcoholic fatty liver disease, and cancer. Exercise training conveys health benefits in populations with or without these chronic conditions. Diet and exercise regulate gene expression by mediating epigenetic mechanisms in many tissues; however, such effects are poorly documented in the liver, a central metabolic organ. To dissect the consequences of diet and exercise on the liver epigenome, we measured DNA methylation, using reduced representation bisulfite sequencing, and transcription, using RNA-seq, in mice maintained on a fast food diet with sedentary lifestyle or exercise, compared with control diet with and without exercise. Our analyses reveal that genome-wide differential DNA methylation and expression of gene clusters are induced by diet and/or exercise. A combination of fast food and exercise triggers extensive gene alterations, with enrichment of carbohydrate/lipid metabolic pathways and muscle developmental processes. Through evaluation of putative protective effects of exercise on diet-induced DNA methylation, we show that hypermethylation is effectively prevented, especially at promoters and enhancers, whereas hypomethylation is only partially attenuated. We assessed diet-induced DNA methylation changes associated with liver cancer-related epigenetic modifications and identified significant increases at liver-specific enhancers in fast food groups, suggesting partial loss of liver cell identity. Hypermethylation at a subset of gene promoters was associated with inhibition of tissue development and promotion of carcinogenic processes. Our study demonstrates extensive reprogramming of the epigenome by diet and exercise, emphasizing the functional relevance of epigenetic mechanisms as an interface between lifestyle modifications and phenotypic alterations.

Indexed as

Animal Nutritional Physiological PhenomenaDiet, High-FatDNA MethylationEpigenesis, GeneticAnimalsFeeding BehaviorGene Expression ProfilingLiverMaleMiceMice, Inbred C57BLMice, TransgenicPhysical Conditioning, AnimalAgingcancerDNA methylationexercisehigh fatNAFLD

Identifiers

PMID27858497
PMCPMC5270632
OpenAlexW2552756389

What OpenQuestion holds

Textmetadata
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.