Evidence map›Paper›PMID 27437034›Full record

ArticleClinical epigenetics2016

Next-generation sequencing methylation profiling of subjects with obesity identifies novel gene changes.

Samantha E Day, Richard L Coletta, Joon Young Kim, Latoya E Campbell, Tonya R Benjamin, Lori R Roust, Elena A De Filippis, Valentin Dinu, Gabriel Q Shaibi, Lawrence J Mandarino and 1 more

Open access · goldAbstract read
In one paragraph

Article in Clinical epigenetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed, 1 pooled it
1.6field-weighted citation impact, top 16% 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

15 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.

  1. Molecular Effects of Physical Activity and Body Composition: A Systematic Review and Meta-Analysis.International journal of environmental research and public health · 2025
    Pooled it
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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

11 authors at 4 institutions in 1 country.

Samantha E DaySchool of Life Sciences, Arizona State University, Tempe, AZ USA.
Richard L ColettaSchool for the Science of Health Care Delivery, Arizona State University, Phoenix, AZ USA.
Joon Young KimDivision of Weight Management and Wellness Children's Hospital of Pittsburgh, Pittsburgh, PA USA.
Latoya E CampbellSchool of Life Sciences, Arizona State University, Tempe, AZ USA.
Tonya R BenjaminEndocrinology Department, Mayo Clinic in Arizona, Scottsdale, AZ USA.
Lori R RoustEndocrinology Department, Mayo Clinic in Arizona, Scottsdale, AZ USA.
Elena A De FilippisEndocrinology Department, Mayo Clinic in Arizona, Scottsdale, AZ USA.
Valentin DinuThe Department of Biomedical Informatics, Arizona State University, Phoenix, AZ USA.
Gabriel Q ShaibiCollege of Nursing and Health Innovation Arizona State University, Phoenix, AZ USA ; Mayo/ASU Center for Metabolic and Vascular Biology, Mayo Clinic in Arizona, Scottsdale, AZ USA.
Lawrence J MandarinoDivision of Endocrinology, Diabetes and Metabolism in the Department of Medicine at the UA College of Medicine, University of Arizona, Tucson, AZ USA.
Dawn K ColettaMayo/ASU Center for Metabolic and Vascular Biology, Mayo Clinic in Arizona, Scottsdale, AZ USA ; School of Nutrition and Health Promotion, College of Health Solutions, Arizona State University, 550 N. 3rd Street, Phoenix, AZ 85004 USA ; Department of Basic Medical Sciences, The University of Arizona College of Medicine, Phoenix, AZ USA.
Arizona State University · USMayo Clinic in Arizona · USChildren's Hospital of Pittsburgh · USUniversity of Arizona · US

Funding

Epigenetics and the Origin of Muscle Insulin Resistance in HumansR01DK094013 · NIDDK · UNIVERSITY OF ARIZONA · PI COLETTA, DAWN KATRINA · 2012 to 2016
$1.9M
NIDDK NIH HHS R01 DK094013NIDDK NIH HHS R01DK094013
6 · The paper itself

Abstract

backgroundObesity is a metabolic disease caused by environmental and genetic factors. However, the epigenetic mechanisms of obesity are incompletely understood. The aim of our study was to investigate the role of skeletal muscle DNA methylation in combination with transcriptomic changes in obesity.

resultsMuscle biopsies were obtained basally from lean (n = 12; BMI = 23.4 ± 0.7 kg/m(2)) and obese (n = 10; BMI = 32.9 ± 0.7 kg/m(2)) participants in combination with euglycemic-hyperinsulinemic clamps to assess insulin sensitivity. We performed reduced representation bisulfite sequencing (RRBS) next-generation methylation and microarray analyses on DNA and RNA isolated from vastus lateralis muscle biopsies. There were 13,130 differentially methylated cytosines (DMC; uncorrected P < 0.05) that were altered in the promoter and untranslated (5' and 3'UTR) regions in the obese versus lean analysis. Microarray analysis revealed 99 probes that were significantly (corrected P < 0.05) altered. Of these, 12 genes (encompassing 22 methylation sites) demonstrated a negative relationship between gene expression and DNA methylation. Specifically, sorbin and SH3 domain containing 3 (SORBS3) which codes for the adapter protein vinexin was significantly decreased in gene expression (fold change -1.9) and had nine DMCs that were significantly increased in methylation in obesity (methylation differences ranged from 5.0 to 24.4 %). Moreover, differentially methylated region (DMR) analysis identified a region in the 5'UTR (Chr.8:22,423,530-22,423,569) of SORBS3 that was increased in methylation by 11.2 % in the obese group. The negative relationship observed between DNA methylation and gene expression for SORBS3 was validated by a site-specific sequencing approach, pyrosequencing, and qRT-PCR. Additionally, we performed transcription factor binding analysis and identified a number of transcription factors whose binding to the differentially methylated sites or region may contribute to obesity.

conclusionsThese results demonstrate that obesity alters the epigenome through DNA methylation and highlights novel transcriptomic changes in SORBS3 in skeletal muscle.

Indexed as

DNA MethylationAdaptor Proteins, Signal TransducingAdultEpigenesis, GeneticFemaleGene Expression ProfilingGene Expression RegulationHigh-Throughput Nucleotide SequencingHumansMaleMuscle ProteinsObesityOligonucleotide Array Sequence AnalysisPromoter Regions, GeneticSequence Analysis, DNASequence Analysis, RNAAdaptor Proteins, Signal TransducingMuscle ProteinsSORBS3 protein, humanMethylationNext-generation sequencingObesitySkeletal muscle

Identifiers

PMID27437034
PMCPMC4950754
OpenAlexW2507026380

What OpenQuestion 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 OpenQuestion graph.