Endothelial cell alterations in capillaries of adipose tissue from patients affected by lipedema.

Pamela Pellegrino, Serena Michelini, Sandro Michelini, Stefania Greco, Pasquapina Ciarmela, Karen L Herbst, Gaia Goteri, Tonia Luca, Sergio Castorina, Angelica Di Vincenzo, Saverio Cinti, Antonio Giordano, Nicola Vaia, Valeria Puleo

Journal: Obesity (Silver Spring, Md.) 2025;33(4):695-708

PMID: 40077894

Abstract

OBJECTIVE

This study aimed to evaluate adipose tissue of lipedema patients.

METHODS

Gluteo-femoral (affected area) and interscapular (nonaffected area) adipose tissue from 10 lean patients affected by lipedema stage 1 to 2 was studied and compared with tissue from 10 patients with obesity and 12 lean patients.

RESULTS

The main features were alterations of capillaries with wall thickening (p ≤ 0.0001), endothelial and pericyte hyperplasia (p = 0.03 and p = 0.004), hypodense areas in basal membrane, and endothelial degeneration with exfoliation of degenerated cells into the capillary lumen. Adipocytes were larger (hypertrophic) in affected (P ≤ 0.0001) and nonaffected (p = 0.0003) areas compared with those with obesity and who were lean (both p ≤ 0.0001). Frequently the cytoplasm of adipocytes contained massive deposition of calcium crystals as revealed by Von Kossa staining (p = 0.023) and electron microscopy. CD68 immunoreactive macrophages were more abundant in affected areas (p = 0.005), and their number was similar to that found in fat from patients with obesity (p = 0.17). Despite adipocyte hypertrophy and inflammation, lack of the healthy marker perilipin-1 and the presence of crown-like structures were only rarely seen, while they were quite frequent in patients with obesity.

CONCLUSIONS

Our data support the idea that cell alterations happen in the early stages of adipocyte development (endothelium/pericyte) in the adipose organ of women affected by lipedema.

© 2025 The Author(s). Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society.

Address: Vascular Diagnostics and Rehabilitation Service, Marino Hospital, Rome, Italy.; Physical Medicine and Rehabilitation, San Giovanni Battista Hospital, Rome, Italy.; Department of Experimental and Clinical Medicine, Center of Obesity, Università Politecnica delle Marche (Polytechnic University of Marche), Ancona, Italy.; Plastic, Reconstructive and Aesthetic Surgery, European Hospital, Rome, Italy.; Department of Science and Public Health, Catholic University Policlinico Gemelli, Rome, Italy.; Physical Medicine and Rehabilitation, San Giovanni Battista Hospital, Rome, Italy.; The Roxbury Institute, Tucson, Arizona, USA.; Department of Biomedical Sciences and Public Health, Section of Pathological Anatomy and Histopathology, Università Politecnica delle Marche (Polytechnic University of Marche), Ancona, Italy.; Department of Medical, Surgical Sciences and Advanced Technologies "G.F. Ingrassia", University of Catania, Catania, Italy.; Department of Experimental and Clinical Medicine, Center of Obesity, Università Politecnica delle Marche (Polytechnic University of Marche), Ancona, Italy.; Istituto di Ricovero e Cura a Carattere Scientifico (Scientific Institute for Research, Hospitalization and Health Care), Istituto Nazionale di Ricovero e Cura per Anziani (National Institute of Hospitalization and Care for the Elderly) (IRCCS/INRCA), Ancona, Italy.

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