Evidence map›Paper›PMID 42304432›Full record

ArticleClinical epigenetics2026

Blood DNA methylation of EIF5A and TGIF1 is associated with adipose tissue health and metabolic outcomes in obesity: a multi-cohort study.

Sophie Ruf, Anne Hoffmann, Luise Müller, Kathrin Landgraf, Mandy Vogel, Emil Jørsboe, Phil Kubitz, Arne Dietrich, Adhideb Ghosh, Falko Noé and 9 more

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Article in Clinical epigenetics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

19 authors.

Sophie RufMedical Department III - Endocrinology, Nephrology and Rheumatology, Leipzig University, Liebigstraße 19, 04103, Leipzig, Germany.
Anne HoffmannHelmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG), Helmholtz Munich at Leipzig University and University of Leipzig Medical Center, Philipp-Rosenthal Str. 27, 04103, Leipzig, Germany.
Luise MüllerMedical Department III - Endocrinology, Nephrology and Rheumatology, Leipzig University, Liebigstraße 19, 04103, Leipzig, Germany.
Kathrin LandgrafHelmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG), Helmholtz Munich at Leipzig University and University of Leipzig Medical Center, Philipp-Rosenthal Str. 27, 04103, Leipzig, Germany.
Mandy VogelCenter for Pediatric Research, Leipzig University, Medical Faculty, University Hospital for Children and Adolescents, Leipzig, Germany.
Emil JørsboeNuffield Department of Population Health, University of Oxford, Oxford, UK.
Phil KubitzElse Kröner-Fresenius-Center for Nutritional Medicine, Chair of Nutritional Medicine, School of Life Sciences, Technical University of Munich, Freising-Weihenstephan, Germany.
Arne DietrichMedical Department of Visceral, Transplantation, Thoracic and Vascular Surgery, University of Leipzig, Leipzig, Germany.
Adhideb GhoshInstitute of Food, Nutrition and Health, ETH Zürich, Schwerzenbach, Switzerland.
Falko NoéInstitute of Food, Nutrition and Health, ETH Zürich, Schwerzenbach, Switzerland.
Christian WolfrumInstitute of Food, Nutrition and Health, ETH Zürich, Schwerzenbach, Switzerland.
Melina ClaussnitzerMedical and Population Genetics Program & Broad Diabetes Initiative, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Hans HaunerElse Kröner-Fresenius-Center for Nutritional Medicine, Chair of Nutritional Medicine, School of Life Sciences, Technical University of Munich, Freising-Weihenstephan, Germany.
Michael StumvollMedical Department III - Endocrinology, Nephrology and Rheumatology, Leipzig University, Liebigstraße 19, 04103, Leipzig, Germany.
Ronny BaberGerman Center for Child and Adolescent Health (DZKJ), Partner Site Leipzig/Dresden, Leipzig, Germany.
Matthias BlüherMedical Department III - Endocrinology, Nephrology and Rheumatology, Leipzig University, Liebigstraße 19, 04103, Leipzig, Germany.
Antje KörnerHelmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG), Helmholtz Munich at Leipzig University and University of Leipzig Medical Center, Philipp-Rosenthal Str. 27, 04103, Leipzig, Germany.
Peter KovacsMedical Department III - Endocrinology, Nephrology and Rheumatology, Leipzig University, Liebigstraße 19, 04103, Leipzig, Germany. peter.kovacs@medizin.uni-leipzig.de.
Maria KellerMedical Department III - Endocrinology, Nephrology and Rheumatology, Leipzig University, Liebigstraße 19, 04103, Leipzig, Germany. maria.keller@helmholtz-munich.de.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundBlood-based DNA methylation has been linked to obesity and metabolic health, yet its relationship to adipose tissue function remains incompletely understood. This study aimed to investigate the epigenetic regulation of EIF5A (Eukaryotic translation initiation factor 5A-1) and TGIF1 (TGFB Induced Factor Homeobox 1) across blood and adipose tissue in obesity.

methodsCandidate genes were identified using a multi-step gene selection approach integrating transcriptomic and epigenomic data from blood and adipose tissue samples obtained from children and adults across four diverse population- and disease-focused cohorts. Genes were prioritized based on differential DNA methylation and gene expression in obesity. Targeted bisulfite sequencing of EIF5A and TGIF1 was conducted in blood samples from adults across BMI-defined groups and from children prior to the development of obesity, to validate candidate loci and to examine associations with metabolic and adipocyte-related phenotypes.

resultsIn adults from the Leipzig Obesity BioBank, blood DNA methylation (N = 150) of both EIF5A and TGIF1 was significantly increased in individuals with obesity. EIF5A mRNA expression (N = 1554) was significantly higher in omental-visceral adipose tissue compared with subcutaneous adipose tissue. Blood DNA methylation of EIF5A was associated with body mass index (BMI), glycated hemoglobin (HbA1c), and leukocyte counts, particularly among individuals with type 2 diabetes mellitus. In children, blood DNA methylation (N = 75) of EIF5A was associated with longitudinal HbA1c trajectories. For TGIF1, DNA methylation levels were increased in subcutaneous adipose tissue (N = 219) of children with obesity and correlated with fasting serum insulin concentrations. Across cohorts, TGIF1 regulation in both blood and adipose tissue showed consistent associations with adipocyte size. Notably, blood DNA methylation of TGIF1 in childhood was associated with body fat mass and HbA1c at later follow-up despite normal weight at baseline.

conclusionEIF5A and TGIF1 DNA methylation represent cross-tissue epigenetic signatures linking blood-based DNA methylation to adipose tissue dysfunction, adipocyte hypertrophy, and early metabolic risk. These findings support the potential of blood DNA methylation markers to reflect adipose tissue health and metabolic outcomes across the lifespan.

Indexed as

Adipose TissueDNA MethylationHomeodomain ProteinsObesityPeptide Initiation FactorsRepressor ProteinsRNA-Binding ProteinsAdultBody Mass IndexChildCohort StudiesEpigenesis, GeneticEukaryotic Translation Initiation Factor 5AFemaleGlycated HemoglobinHumansEukaryotic Translation Initiation Factor 5AGlycated HemoglobinHomeodomain ProteinsPeptide Initiation FactorsRepressor ProteinsRNA-Binding ProteinsTGIF1 protein, humanAdipose tissueBloodChildhoodDNA methylationEpigeneticsMetabolismmRNA expressionObesity

Identifiers

PMID42304432
PMCPMC13274240

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