Evidence mapPaperPMID 41580786Full record

ArticleJournal of translational medicine2026

Epigenetic alterations of AKT1 orchestrate a metabolic reprogramming in advanced lipedema: translational insights from an integrated multi-omics study.

Biagio Santella, Annamaria Salvati, Alexander Papp, Annamaria D'Ursi, Domenico Memoli, Monica Mingo, Christoph Pulai, Carmen Marino, Luca Rastrelli, Maria D'Elia and 2 more

Abstract read
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Article in Journal of translational medicine, 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

Who cites it

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No citing paper in PubMed yet.

4 · The record

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5 · Who and what money

Authors and funding

12 authors.

Biagio Santella *Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana", University of Salerno, Baronissi, Salerno, 84081, Italy.
Annamaria Salvati *Laboratory of Molecular Medicine and Genomics, Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana", University of Salerno, Baronissi, Salerno, Italy.
Alexander PappP-Health Medical Solution, F.-W.-Raiffeisenstraße 1b, Elsbethen, Salzburg, 5061, Austria.
Annamaria D'UrsiNational Biodiversity Future Center (NBFC), Palermo, 90133, Italy.
Domenico MemoliLaboratory of Molecular Medicine and Genomics, Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana", University of Salerno, Baronissi, Salerno, Italy.
Monica MingoDepartment of Medicine, Surgery and Dentistry "Scuola Medica Salernitana", University of Salerno, Baronissi, Salerno, 84081, Italy.
Christoph PulaiP-Health Medical Solution, F.-W.-Raiffeisenstraße 1b, Elsbethen, Salzburg, 5061, Austria.
Carmen MarinoDepartment of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, Fisciano, Salerno, 84084, Italy.
Luca RastrelliNational Biodiversity Future Center (NBFC), Palermo, 90133, Italy.
Maria D'EliaNational Biodiversity Future Center (NBFC), Palermo, 90133, Italy.
Giovanni NassaLaboratory of Molecular Medicine and Genomics, Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana", University of Salerno, Baronissi, Salerno, Italy. gnassa@unisa.it.
Luigi SchiavoDepartment of Medicine, Surgery and Dentistry "Scuola Medica Salernitana", University of Salerno, Baronissi, Salerno, 84081, Italy. lschiavo@unisa.it.ORCID http://orcid.org/0000-0003-3639-6847

Funding

National Biodiversity Future Center CN00000033PNRR-MUR NextGenerationEU PRIN 2022 D53D23007790001PNRR-MUR NextGenerationEU PRIN-PNRR 2022 D53D23016530001
6 · The paper itself

Abstract

backgroundlipedema is a chronic, progressive adipose disorder predominantly affecting women, characterized by painful, symmetrical subcutaneous fat accumulation, and typically resistant to lifestyle interventions. The pathophysiology of advanced-stage lipedema remains poorly defined, and no validated biomarkers or targeted therapies are currently available.

methodsin this observational study, we applied a comprehensive multi-omics approach to dissect the molecular and metabolic alterations underlying late-stage lipedema.

resultsGenome-wide DNA methylation profiling identified over 5,000 differentially methylated CpG sites affecting genes involved in receptor tyrosine kinase signaling, phospho-metabolism, and immune pathways. Transcriptomic analysis revealed profound downregulation of mitochondrial functions, including oxidative phosphorylation, the TCA cycle, and fatty acid β-oxidation, alongside disruption of the sirtuin pathway and extracellular matrix remodeling. Integrative analysis pinpointed AKT1 as a central regulatory node: its promoter region was hypomethylated, correlating with increased gene expression and protein phosphorylation. Metabolomic profiling confirmed AKT1-linked metabolic dysregulation, including altered levels of L-arginine, NADP+, ATP, guanosine, glycerol, and glutamate, indicating impaired redox balance and energy metabolism. Trans-omic network analysis positioned AKT1 at the intersection of multiple dysregulated pathways, suggesting its key role in advanced-stage lipedema.

conclusionsthe consistent enhancing of AKT pathway signaling across omic layers highlights its potential not only as a biomarker for disease stratification but also as a putative druggable target for therapeutic intervention. These findings offer new mechanistic insights into lipedema pathophysiology and provide a rationale for future personalized treatment strategies guided by AKT1-centric molecular profiling.

Indexed as

Epigenesis, GeneticMetabolic ReprogrammingProto-Oncogene Proteins c-aktDNA MethylationFemaleGene Expression ProfilingHumansMultiomicsSignal TransductionAKT1 protein, humanProto-Oncogene Proteins c-aktAKT1 signalingDNA methylationEpigenetic regulationLipedemaMitochondrial dysfunctionMulti-omics integration

Identifiers

PMID41580786
PMCPMC12911300

What Socratic holds

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LicenceCC BY-NC-ND
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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 Socratic graph.