Lipedema is one of the most often underdiagnosed conditions among subcutaneous adipose tissue (SAT) accumulation-related disorders. Lipedema is characterized by disproportional, bilateral and symmetrical SAT deposition mostly in lower extremities and arms. It mainly affects women, especially during phases of hormonal changes (e.g. pregnancy, menopause). Weight-loss interventions are not effective in reducing lipedema SAT mass which is also characterised as painful fat. An autosomal dominance with incomplete penetrance is the proposed inheritance pattern for lipedema onset, although no specific lipedema genes have been indentified to date. Moreover, the mechanisms associated with lipedema progression and clinical manifestation are unknown, as well as circulating biomarkers to support its diagnosis.

Here, we aim to identify gene(s) involved in lipedema inheritability by whole genome sequencing as well as to characterize metabolic and molecular alterations specific to this condition. In a first proteomic approach, we have identified a panel of upregulated circulating inflammatory proteins which could play a mechanistic role and may serve as biomarkers for the diagnosis of lipedema in clinical practice. We also found a preserved glycemic control in lipedema patients despite the subclinical activation of proinflammatory signals. We are testing the hypothesis that lipedema may serve as a model to investigate mechanisms linking SAT expansion to cardio-metabolic risk. Subsequent analyses of lipedema-affected SAT structure and function using histological, transcriptomic and single-cell approaches are ongoing.