Evidence map›Paper›PMID 25565211›Full record

ArticleCell metabolism2015

Mouse-human experimental epigenetic analysis unmasks dietary targets and genetic liability for diabetic phenotypes.

Michael L Multhaup, Marcus M Seldin, Andrew E Jaffe, Xia Lei, Henriette Kirchner, Prosenjit Mondal, Yuanyuan Li, Varenka Rodriguez, Alexander Drong, Mehboob Hussain and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell metabolism, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
67citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

67 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  14. Aging and obesity prime the methylome and transcriptome of adipose stem cells for disease and dysfunction.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023
    Article
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  16. Article
  17. Obesity elicits a unique metabolomic signature in human airway smooth muscle cells.American journal of physiology. Lung cellular and molecular physiology · 2022
    Article
  18. Article
  19. Epigenetics in Precision Nutrition.Journal of personalized medicine · 2022
    Review
  20. Review

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors.

Michael L MulthaupDepartment of Medicine, Johns Hopkins University School of Medicine, 855 North Wolfe Street, Baltimore, MD 21205, USA; Center for Epigenetics, Johns Hopkins University School of Medicine, 855 North Wolfe Street, Baltimore, MD 21205, USA.
Marcus M SeldinDepartment of Physiology, Johns Hopkins University School of Medicine, 855 North Wolfe Street, Baltimore, MD 21205, USA; Center for Metabolism and Obesity Research, Johns Hopkins University School of Medicine, 855 North Wolfe Street, Baltimore, MD 21205, USA.
Andrew E JaffeLieber Institute for Brain Development, 855 North Wolfe Street, Baltimore, MD 21205, USA; Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, MD 21205, USA.
Xia LeiDepartment of Physiology, Johns Hopkins University School of Medicine, 855 North Wolfe Street, Baltimore, MD 21205, USA; Center for Metabolism and Obesity Research, Johns Hopkins University School of Medicine, 855 North Wolfe Street, Baltimore, MD 21205, USA.
Henriette KirchnerDepartment of Molecular Medicine and Surgery Karolinska Institutet, 171 77 Stockholm, Sweden.
Prosenjit MondalDepartment of Pediatrics, Johns Hopkins University School of Medicine, 855 North Wolfe Street, Baltimore, MD 21205, USA.
Yuanyuan LiDepartment of Pediatrics, Johns Hopkins University School of Medicine, 855 North Wolfe Street, Baltimore, MD 21205, USA.
Varenka RodriguezDepartment of Medicine, Johns Hopkins University School of Medicine, 855 North Wolfe Street, Baltimore, MD 21205, USA; Center for Epigenetics, Johns Hopkins University School of Medicine, 855 North Wolfe Street, Baltimore, MD 21205, USA.
Alexander DrongWellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.
Mehboob HussainDepartment of Pediatrics, Johns Hopkins University School of Medicine, 855 North Wolfe Street, Baltimore, MD 21205, USA.
Cecilia LindgrenWellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.
Mark McCarthyWellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK; Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Old Road, Headington, Oxford OX3 7LI, UK; Oxford NIHR Biomedical Research Centre, Churchill Hospital, Old Road, Headington, Oxford OX3 7LI, UK.
Erik NäslundDepartment of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, 182 88 Stockholm, Sweden.
Juleen R ZierathDepartment of Molecular Medicine and Surgery Karolinska Institutet, 171 77 Stockholm, Sweden.
G William WongDepartment of Physiology, Johns Hopkins University School of Medicine, 855 North Wolfe Street, Baltimore, MD 21205, USA; Center for Metabolism and Obesity Research, Johns Hopkins University School of Medicine, 855 North Wolfe Street, Baltimore, MD 21205, USA.
Andrew P FeinbergDepartment of Medicine, Johns Hopkins University School of Medicine, 855 North Wolfe Street, Baltimore, MD 21205, USA; Center for Epigenetics, Johns Hopkins University School of Medicine, 855 North Wolfe Street, Baltimore, MD 21205, USA. Electronic address: afeinberg@jhu.edu.

Funding

BIOCHEMISTRY, CELLULAR AND MOLECULAR BIOLOGY PROGRAMT32GM007445 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI GREEN, RACHEL · 1985 to 2021
$24.1M
Training Program in Cellular and Molecular MedicineT32GM008752 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI RAO, RAJINI · 2000 to 2019
$11.7M
JHU-UMD Diabetes Research CenterP30DK079637 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI AHIMA, REXFORD S. · 2013 to 2017
$9.7M
CTRP and Metabolic ControlR01DK084171 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI Guang William Wong · 2010 to 2026
$8.0M
A General Stochastic Epigenetic Model for Evolution, Development, and DiseaseDP1ES022579 · NIEHS · JOHNS HOPKINS UNIVERSITY · PI FEINBERG, ANDREW P. · 2012 to 2015
$3.2M
Beta-cell ProliferationR01DK081472 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI HUSSAIN, MEHBOOB A, WONDISFORD, FREDRIC E. · 2009 to 2013
$2.1M
Hepatic endocrine suppression of the pancreatic beta-cellR01DK101591 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI HUSSAIN, MEHBOOB A, WOLFE, ANDREW M · 2014 to 2017
$2.0M
NIDDK NIH HHS P30 DK079637NIDDK NIH HHS R01 DK081472NIDDK NIH HHS R01 DK084171NIDDK NIH HHS R01 DK101591NIEHS NIH HHS DP1 ES022579NIGMS NIH HHS T32 GM007445NIGMS NIH HHS T32 GM008752
6 · The paper itself

Abstract

Using a functional approach to investigate the epigenetics of type 2 diabetes (T2D), we combine three lines of evidence-diet-induced epigenetic dysregulation in mouse, epigenetic conservation in humans, and T2D clinical risk evidence-to identify genes implicated in T2D pathogenesis through epigenetic mechanisms related to obesity. Beginning with dietary manipulation of genetically homogeneous mice, we identify differentially DNA-methylated genomic regions. We then replicate these results in adipose samples from lean and obese patients pre- and post-Roux-en-Y gastric bypass, identifying regions where both the location and direction of methylation change are conserved. These regions overlap with 27 genetic T2D risk loci, only one of which was deemed significant by GWAS alone. Functional analysis of genes associated with these regions revealed four genes with roles in insulin resistance, demonstrating the potential general utility of this approach for complementing conventional human genetic studies by integrating cross-species epigenomics and clinical genetic risk.

Indexed as

Epigenesis, GeneticAdipocytesAnimalsCells, CulturedDiabetes Mellitus, Type 2Diet, High-FatDNA MethylationGene Expression RegulationGenetic LociGenome-Wide Association StudyGlucose Tolerance TestHumansMaleMiceMice, Inbred C57BLPolymorphism, Single NucleotideRNA, Small InterferingTCF7L2 protein, humanTranscription Factor 7-Like 2 Protein

Identifiers

PMID25565211
PMCPMC4340475

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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 OpenQuestion graph.