biostudies-literatureSantella BPNRR-MUR NextGenerationEU PRIN-PNRR 2022PNRR-MUR NextGenerationEU PRIN 2022National Biodiversity Future Center265https://www.ebi.ac.uk/biostudies/studies/S-EPMC12911300biostudies-literatureUnknown24(1)<h4>Background</h4>lipedema 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.<h4>Methods</h4>in this observational study, we applied a comprehensive multi-omics approach to dissect the molecular and metabolic alterations underlying late-stage lipedema.<h4>Results</h4>Genome-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 profounJournal of translational medicineEpigenetic alterations of AKT1 orchestrate a metabolic reprogramming in advanced lipedema: translational insights from an integrated multi-omics study.PMC12911300CN00000033D53D23007790001D53D23016530001Schiavo LSalvati ANassa GMemoli DMarino CPulai CD'Elia MD'Ursi AMingo MSantella BPapp ARastrelli LfalseEpigenetic alterations of AKT1 orchestrate a metabolic reprogramming in advanced lipedema: translational insights from an integrated multi-omics study.<h4>Background</h4>lipedema 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.<h4>Methods</h4>in this observational study, we applied a comprehensive multi-omics approach to dissect the molecular and metabolic alterations underlying late-stage lipedema.<h4>Results</h4>Genome-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 profoun2026-01-01T00:00:00Z2026 Jan2026-07-16T04:58:59.865Z2026-07-09T13:10:03.058ZS-EPMC129113004158078610.1186/s12967-026-07726-w