Evidence map›Paper›PMID 33933146›Full record

ArticleClinical epigenetics2021

Weight loss after Roux-En-Y gastric bypass surgery reveals skeletal muscle DNA methylation changes.

Luis A Garcia, Samantha E Day, Richard L Coletta, Baltazar Campos, Tonya R Benjamin, Eleanna De Filippis, James A Madura, Lawrence J Mandarino, Lori R Roust, Dawn K Coletta

Open access · goldAbstract read
In one paragraph

Article in Clinical epigenetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
6.9field-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

8 citing papers in PubMed, 17 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

10 authors at 4 institutions in 1 country.

Luis A GarciaDepartment of Medicine, Division of Endocrinology, The University of Arizona College of Medicine, 1501 N. Campbell Ave, PO Box 245035, Tucson, AZ, 85724-5035, USA.
Samantha E DayPhoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, AZ, USA.
Richard L ColettaDepartment of Medicine, Division of Endocrinology, The University of Arizona College of Medicine, 1501 N. Campbell Ave, PO Box 245035, Tucson, AZ, 85724-5035, USA.
Baltazar CamposDepartment of Medicine, Division of Endocrinology, The University of Arizona College of Medicine, 1501 N. Campbell Ave, PO Box 245035, Tucson, AZ, 85724-5035, USA.
Tonya R BenjaminDepartment of Endocrinology, Metabolism and Diabetes, Mayo Clinic Arizona, Scottsdale, AZ, USA.
Eleanna De FilippisDepartment of Endocrinology, Metabolism and Diabetes, Mayo Clinic Arizona, Scottsdale, AZ, USA.
James A MaduraMayo Clinic Hospital, Phoenix, AZ, USA.
Lawrence J MandarinoDepartment of Medicine, Division of Endocrinology, The University of Arizona College of Medicine, 1501 N. Campbell Ave, PO Box 245035, Tucson, AZ, 85724-5035, USA.
Lori R RoustDepartment of Endocrinology, Metabolism and Diabetes, Mayo Clinic Arizona, Scottsdale, AZ, USA.
Dawn K ColettaDepartment of Medicine, Division of Endocrinology, The University of Arizona College of Medicine, 1501 N. Campbell Ave, PO Box 245035, Tucson, AZ, 85724-5035, USA. dcoletta@email.arizona.edu.ORCID 0000-0001-5819-5152
University of Arizona · USMayo Clinic in Arizona · USMayo Clinic Hospital · USNational Institutes of Health · US

Funding

SOUTHWEST ENVIRONMENTAL HEALTH SCIENCES CENTERP30ES006694 · NIEHS · UNIVERSITY OF ARIZONA · PI DEAN BILLHEIMER · 1994 to 2026
$36.7M
ZESTRIL VS. VERAPAMIL IN THE TREATMENT OF HYPERTENSIONM01RR000585 · NCRR · MAYO CLINIC ROCHESTER · PI RIZZA, ROBERT A. · 1985 to 2006
$30.4M
Institutional Career Development CoreKL2TR002379 · NCATS · MAYO CLINIC ROCHESTER · PI NILUFER ERTEKIN-TANER · 2017 to 2026
$14.9M
Epigenetics and the Origin of Muscle Insulin Resistance in HumansR01DK094013 · NIDDK · UNIVERSITY OF ARIZONA · PI COLETTA, DAWN KATRINA · 2012 to 2016
$1.9M
NCATS NIH HHS KL2 TR002379NCRR NIH HHS M01 RR000585NIDDK NIH HHS R01 DK094013NIEHS NIH HHS P30 ES006694
6 · The paper itself

Abstract

backgroundThe mechanisms of weight loss and metabolic improvements following bariatric surgery in skeletal muscle are not well known; however, epigenetic modifications are likely to contribute. The aim of our study was to investigate skeletal muscle DNA methylation after weight loss induced by Roux-en-Y gastric bypass (RYGB) surgery. Muscle biopsies were obtained basally from seven insulin-resistant obese (BMI > 40 kg/m

resultsGlobal methylation was significantly higher in the pre- (32.97 ± 0.02%) and post-surgery (33.31 ± 0.02%) compared to the lean (30.46 ± 0.02%), P < 0.05. MethylSig analysis identified 117 differentially methylated cytosines (DMCs) that were significantly altered in the post- versus pre-surgery (Benjamini-Hochberg q < 0.05). In addition, 2978 DMCs were significantly altered in the pre-surgery obese versus the lean controls (Benjamini-Hochberg q < 0.05). For the post-surgery obese versus the lean controls, 2885 DMCs were altered (Benjamini-Hochberg q < 0.05). Seven post-surgery obese DMCs were normalized to levels similar to those observed in lean controls. Of these, 5 were within intergenic regions (chr11.68,968,018, chr16.73,100,688, chr5.174,115,531, chr5.1,831,958 and chr9.98,547,011) and the remaining two DMCs chr17.45,330,989 and chr14.105,353,824 were within in the integrin beta 3 (ITGB3) promoter and KIAA0284 exon, respectively. ITGB3 methylation was significantly decreased in the post-surgery (0.5 ± 0.5%) and lean controls (0 ± 0%) versus pre-surgery (13.6 ± 2.7%, P < 0.05). This decreased methylation post-surgery was associated with an increase in ITGB3 gene expression (fold change + 1.52, P = 0.0087). In addition, we showed that ITGB3 promoter methylation in vitro significantly suppressed transcriptional activity (P < 0.05). Transcription factor binding analysis for ITGB3 chr17.45,330,989 identified three putative transcription factor binding motifs; PAX-5, p53 and AP-2alphaA.

conclusionsThese results demonstrate that weight loss after RYGB alters the epigenome through DNA methylation. In particular, this study highlights ITGB3 as a novel gene that may contribute to the metabolic improvements observed post-surgery. Future additional studies are warranted to address the exact mechanism of ITGB3 in skeletal muscle.

Indexed as

DNA MethylationEpigenesis, GeneticFemaleGastric BypassHumansMiddle AgedMuscle, SkeletalObesityWeight LossBariatric surgeryDNA methylationNext generation sequencingObesitySkeletal muscle

Identifiers

PMID33933146
PMCPMC8088644
OpenAlexW3159310568

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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.