Lipedema is increasingly recognized as a systemic adipofascial disorder that predominantly affects women and resists standard weight-loss approaches. This review integrates histology, imaging, and multi-omics evidence to portray lipedema fat as a hypertrophic–hyperplastic depot encased in a stiff, sodium-laden extracellular matrix, with capillary leak, micro-inflammation, and early lymphatic dysfunction perpetuating edema and pain. Omics signatures—spanning exosomal miRNAs, cytokines, lipidomics, and metabolomics—consistently separate lipedema from obesity and lymphedema, while preliminary genetic data implicate both rare missense variants (e.g., AKR1C1-L213Q) and chromosomal aberrations in pathways governing adipocyte proliferation, matrix remodeling, and vascular integrity. Although sample sizes remain small, these molecular clues point toward biomarker-driven diagnostics and etiology-targeted therapy. The authors argue that future interventions must tackle extracellular-matrix remodeling, interstitial-fluid overload, and angiolymphatic repair in tandem, and they highlight emerging technologies—such as focused drug delivery and advanced imaging—to close current therapeutic gaps. 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
