Emerging research reframes lipedema as a systemic adipofascial disease rather than a cosmetic fat surplus. This comprehensive review collates histological and multi-omics data, revealing hypertrophic-hyperplastic adipocytes embedded in a stiff, sodium-rich extracellular matrix, with perivascular fibrosis and low-grade inflammation that impair microcirculation. Dysregulated interstitial-fluid dynamics—driven by leaky capillaries and weakened initial lymphatics—fuel a vicious cycle of edema-induced adipogenesis and pain. Omics signatures (exosomal miRNAs, cytokine panels, lipidomics, metabolomics) increasingly differentiate lipedema from obesity or lymphedema and highlight candidate biomarkers for early diagnosis. Preliminary genetic screens implicate both syndromic chromosomal aberrations and rare missense variants (e.g., AKR1C1-L213Q) in pathways governing adipocyte proliferation, ECM turnover and vascular integrity, but cohort sizes remain too small for definitive risk loci. Therapeutically, the authors argue that effective interventions must target fluid overload, ECM remodeling and angiolymphatic repair—areas where emerging imaging tools, molecular targeting and focused drug-delivery technologies may yield breakthroughs. By synthesizing morphological, molecular and clinical evidence, this review outlines a research roadmap aimed at bridging current knowledge gaps and delivering etiology-guided care for patients. (pubmed.ncbi.nlm.nih.gov)
Ankita Poojari – Department of Physiology & Pharmacology, Thomas J. Long School of Pharmacy, University of the Pacific, Stockton CA, USA
Kapil Dev – Department of Physiology & Pharmacology, Thomas J. Long School of Pharmacy, University of the Pacific, Stockton CA, USA
Atefeh Rabiee – Department of Physiology & Pharmacology, Thomas J. Long School of Pharmacy, University of the Pacific, Stockton CA, USA
Tags: Adipose Tissue; Chronic Disease; Fat Disorder; Lipedema; Lymphedema; Obesity
