Dilated Blood and Lymphatic Microvessels, Angiogenesis, Increased Macrophages, and Adipocyte Hypertrophy in Lipedema Thigh Skin and Fat Tissue

Background and Aim. Lipedema is a common painful SAT disorder characterized by enlargement of fat primarily in the legs of women. Case reports of lipedema tissue samples demonstrate fluid and fibrosis in the interstitial matrix, increased macrophages, and adipocyte hypertrophy. The aims of this proj...

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Main Authors: Sara AL-Ghadban, Walter Cromer, Marisol Allen, Christopher Ussery, Michael Badowski, David Harris, Karen L. Herbst
Format: Article
Language:English
Published: Wiley 2019-01-01
Series:Journal of Obesity
Online Access:http://dx.doi.org/10.1155/2019/8747461
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author Sara AL-Ghadban
Walter Cromer
Marisol Allen
Christopher Ussery
Michael Badowski
David Harris
Karen L. Herbst
author_facet Sara AL-Ghadban
Walter Cromer
Marisol Allen
Christopher Ussery
Michael Badowski
David Harris
Karen L. Herbst
author_sort Sara AL-Ghadban
collection DOAJ
description Background and Aim. Lipedema is a common painful SAT disorder characterized by enlargement of fat primarily in the legs of women. Case reports of lipedema tissue samples demonstrate fluid and fibrosis in the interstitial matrix, increased macrophages, and adipocyte hypertrophy. The aims of this project are to investigate blood vasculature, immune cells, and structure of lipedema tissue in a cohort of women. Methods. Forty-nine participants, 19 controls and 30 with lipedema, were divided into groups based on body mass index (BMI): Non-Obese (BMI 20 to <30 kg/m2) and Obese (BMI 30 to <40 kg/m2). Histological sections from thigh skin and fat were stained with H&E. Adipocyte area and blood vessel size and number were quantified using ImageJ software. Markers for macrophages (CD68), mast cells (CD117), T cells (CD3), endothelial cells (CD31), blood (SMA), and lymphatic (D2-40 and Lyve-1) vessels were investigated by IHC and IF. Results. Non-Obese Lipedema adipocyte area was larger than Non-Obese Controls (p=0.005) and similar to Obese Lipedema and Obese Controls. Macrophage numbers were significantly increased in Non-Obese (p<0.005) and Obese (p<0.05) Lipedema skin and fat compared to Control groups. No differences in T lymphocytes or mast cells were observed when comparing Lipedema to Control in both groups. SMA staining revealed increased dermal vessels in Non-Obese Lipedema patients (p<0.001) compared to Non-Obese Controls. Lyve-1 and D2-40 staining showed a significant increase in lymphatic vessel area but not in number or perimeter in Obese Lipedema participants (p<0.05) compared to Controls (Obese and Non-Obese). Areas of angiogenesis were found in the fat in 30% of lipedema participants but not controls. Conclusion. Hypertrophic adipocytes, increased numbers of macrophages and blood vessels, and dilation of capillaries in thigh tissue of non-obese women with lipedema suggest inflammation, and angiogenesis occurs independent of obesity and demonstrates a role of altered vasculature in the manifestation of the disease.
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spelling doaj-art-0e106d8394ea4e3b89aba4b2937b52ea2025-08-20T03:54:29ZengWileyJournal of Obesity2090-07082090-07162019-01-01201910.1155/2019/87474618747461Dilated Blood and Lymphatic Microvessels, Angiogenesis, Increased Macrophages, and Adipocyte Hypertrophy in Lipedema Thigh Skin and Fat TissueSara AL-Ghadban0Walter Cromer1Marisol Allen2Christopher Ussery3Michael Badowski4David Harris5Karen L. Herbst6Department of Medicine and TREAT Program, College of Medicine, University of Arizona, Tucson, Arizona, USADepartment of Medical Physiology, Texas A&M University Health Science Center, Temple, Texas, USADepartment of Medicine and TREAT Program, College of Medicine, University of Arizona, Tucson, Arizona, USADepartment of Medicine and TREAT Program, College of Medicine, University of Arizona, Tucson, Arizona, USADepartment of Immunobiology and Biorepository, College of Medicine, University of Arizona, Tucson, Arizona, USADepartment of Immunobiology and Biorepository, College of Medicine, University of Arizona, Tucson, Arizona, USADepartment of Medicine and TREAT Program, College of Medicine, University of Arizona, Tucson, Arizona, USABackground and Aim. Lipedema is a common painful SAT disorder characterized by enlargement of fat primarily in the legs of women. Case reports of lipedema tissue samples demonstrate fluid and fibrosis in the interstitial matrix, increased macrophages, and adipocyte hypertrophy. The aims of this project are to investigate blood vasculature, immune cells, and structure of lipedema tissue in a cohort of women. Methods. Forty-nine participants, 19 controls and 30 with lipedema, were divided into groups based on body mass index (BMI): Non-Obese (BMI 20 to <30 kg/m2) and Obese (BMI 30 to <40 kg/m2). Histological sections from thigh skin and fat were stained with H&E. Adipocyte area and blood vessel size and number were quantified using ImageJ software. Markers for macrophages (CD68), mast cells (CD117), T cells (CD3), endothelial cells (CD31), blood (SMA), and lymphatic (D2-40 and Lyve-1) vessels were investigated by IHC and IF. Results. Non-Obese Lipedema adipocyte area was larger than Non-Obese Controls (p=0.005) and similar to Obese Lipedema and Obese Controls. Macrophage numbers were significantly increased in Non-Obese (p<0.005) and Obese (p<0.05) Lipedema skin and fat compared to Control groups. No differences in T lymphocytes or mast cells were observed when comparing Lipedema to Control in both groups. SMA staining revealed increased dermal vessels in Non-Obese Lipedema patients (p<0.001) compared to Non-Obese Controls. Lyve-1 and D2-40 staining showed a significant increase in lymphatic vessel area but not in number or perimeter in Obese Lipedema participants (p<0.05) compared to Controls (Obese and Non-Obese). Areas of angiogenesis were found in the fat in 30% of lipedema participants but not controls. Conclusion. Hypertrophic adipocytes, increased numbers of macrophages and blood vessels, and dilation of capillaries in thigh tissue of non-obese women with lipedema suggest inflammation, and angiogenesis occurs independent of obesity and demonstrates a role of altered vasculature in the manifestation of the disease.http://dx.doi.org/10.1155/2019/8747461
spellingShingle Sara AL-Ghadban
Walter Cromer
Marisol Allen
Christopher Ussery
Michael Badowski
David Harris
Karen L. Herbst
Dilated Blood and Lymphatic Microvessels, Angiogenesis, Increased Macrophages, and Adipocyte Hypertrophy in Lipedema Thigh Skin and Fat Tissue
Journal of Obesity
title Dilated Blood and Lymphatic Microvessels, Angiogenesis, Increased Macrophages, and Adipocyte Hypertrophy in Lipedema Thigh Skin and Fat Tissue
title_full Dilated Blood and Lymphatic Microvessels, Angiogenesis, Increased Macrophages, and Adipocyte Hypertrophy in Lipedema Thigh Skin and Fat Tissue
title_fullStr Dilated Blood and Lymphatic Microvessels, Angiogenesis, Increased Macrophages, and Adipocyte Hypertrophy in Lipedema Thigh Skin and Fat Tissue
title_full_unstemmed Dilated Blood and Lymphatic Microvessels, Angiogenesis, Increased Macrophages, and Adipocyte Hypertrophy in Lipedema Thigh Skin and Fat Tissue
title_short Dilated Blood and Lymphatic Microvessels, Angiogenesis, Increased Macrophages, and Adipocyte Hypertrophy in Lipedema Thigh Skin and Fat Tissue
title_sort dilated blood and lymphatic microvessels angiogenesis increased macrophages and adipocyte hypertrophy in lipedema thigh skin and fat tissue
url http://dx.doi.org/10.1155/2019/8747461
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