Abstract / Summary
Aim: This narrative review summarises evidence on pathogenetic mechanisms of adipose tissue remodelling and adipokine dysregulation in lipedema, focusing on adipocyte hypertrophy and hyperplasia, fibrosis, microcirculatory and lymphatic dysfunction, immune-cell alterations, and diagnostic biomarkers. Methods: We conducted a narrative search in PubMed, Scopus, and Google Scholar from database inception to September 2026, including publications from 2001 to 2026. Search terms included “lipedema”, “lipedema adipokines”, “lipedema biomarkers”, “adipose tissue remodelling”, “fibrosis”, “adipocyte hypertrophy”, and “adipocyte hyperplasia”, combined with specific molecules. Bibliographies were screened. This review was not registered and did not follow a systematic-review protocol. Results: Lipedema involves pathological subcutaneous adipose tissue remodelling, including adipocyte hypertrophy and hyperplasia, extracellular matrix fibrosis, vascular alterations, and lymphatic dysfunction. Adipose tissue macrophages are enriched in CD163+/CD206+ populations, although the M1/M2 framework inadequately represents their heterogeneity. Individual adipokines (leptin, adipocyte-type fatty acid-binding protein) show limited diagnostic value due to dependence on total adipose mass and BMI. Multicomponent signatures (adiponectin, adipocyte-type fatty acid-binding protein, fibroblast growth factor 21, chemerin, afamin, growth and differentiation factor 15) demonstrate promising performance. Additional markers include reduced tissue adipsin expression, altered endostatin, and elevated interleukin-11, interleukin-28A, and interleukin-29. Most studies are limited by small cohorts, cross-sectional designs, inconsistent controls, obesity-related confounding, and lack of external validation. Conclusions: Lipedema involves coordinated metabolic, inflammatory, vascular, and extracellular-matrix alterations. Single adipokines are unreliable diagnostic biomarkers. Multicomponent panels may improve differentiation from obesity, but remain exploratory. Larger multicentre studies with standardised phenotyping and external validation are needed before clinical implementation.