Lipedema stage affects adipocyte hypertrophy, subcutaneous adipose tissue inflammation and interstitial fibrosis

IntroductionLipedema is a painful subcutaneous adipose tissue (SAT) disease characterized by adipocyte hypertrophy, immune cell recruitment, and fibrosis in the affected areas. These features are thought to contribute to the development and progression of the condition. However, the relationship bet...

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Main Authors: Philipp Kruppa, Sabrina Gohlke, Kamila Łapiński, Francisco Garcia-Carrizo, George A. Soultoukis, Manfred Infanger, Tim J. Schulz, Mojtaba Ghods
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-07-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2023.1223264/full
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author Philipp Kruppa
Philipp Kruppa
Philipp Kruppa
Sabrina Gohlke
Kamila Łapiński
Kamila Łapiński
Kamila Łapiński
Francisco Garcia-Carrizo
Francisco Garcia-Carrizo
George A. Soultoukis
Manfred Infanger
Tim J. Schulz
Tim J. Schulz
Tim J. Schulz
Mojtaba Ghods
author_facet Philipp Kruppa
Philipp Kruppa
Philipp Kruppa
Sabrina Gohlke
Kamila Łapiński
Kamila Łapiński
Kamila Łapiński
Francisco Garcia-Carrizo
Francisco Garcia-Carrizo
George A. Soultoukis
Manfred Infanger
Tim J. Schulz
Tim J. Schulz
Tim J. Schulz
Mojtaba Ghods
author_sort Philipp Kruppa
collection DOAJ
description IntroductionLipedema is a painful subcutaneous adipose tissue (SAT) disease characterized by adipocyte hypertrophy, immune cell recruitment, and fibrosis in the affected areas. These features are thought to contribute to the development and progression of the condition. However, the relationship between lipedema disease stage and the associated adipose tissue changes has not been determined so far.MethodsSAT biopsies of 32 lipedema patients, ranging across the pathological stages I to III, and 14 BMI- and age-matched controls were harvested from lipedema-affected thighs and non-symptomatic lower abdominal regions. Histological and immunohistochemical (IHC) staining and expression analysis of markers for adipogenesis, immunomodulation, and fibrosis were performed on the tissue biopsies.ResultsLipedema patients showed increased adipocyte areas and a stage-dependent shift towards larger cell sizes in the thighs. Lipedema SAT was linked with increased interstitial collagen accumulation in the thighs, but not the lower abdominal region when compared to controls. There was a trend toward progressive SAT fibrosis of the affected thighs with increasing lipedema stage. Elevated gene expression levels of macrophage markers were found for thigh SAT biopsies, but not in the abdominal region. IHC staining of lipedema thigh biopsies confirmed a transiently elevated macrophage polarization towards an M2-like (anti-inflammatory) phenotype.ConclusionsIn summary, lipedema SAT is associated with stage-dependent adipocyte hypertrophy, stage-progressive interstitial fibrosis and elevated proportion of M2-like macrophages. The character of the inflammatory response differs from primary obesity and may possess an essential role in the development of lipedema.
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spelling doaj.art-26e0f20e55f94d18bd6080eafae69bb12023-07-28T16:41:37ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-07-011410.3389/fimmu.2023.12232641223264Lipedema stage affects adipocyte hypertrophy, subcutaneous adipose tissue inflammation and interstitial fibrosisPhilipp Kruppa0Philipp Kruppa1Philipp Kruppa2Sabrina Gohlke3Kamila Łapiński4Kamila Łapiński5Kamila Łapiński6Francisco Garcia-Carrizo7Francisco Garcia-Carrizo8George A. Soultoukis9Manfred Infanger10Tim J. Schulz11Tim J. Schulz12Tim J. Schulz13Mojtaba Ghods14Department of Plastic, Aesthetic and Reconstructive Microsurgery/Hand Surgery, Hospital Ernst von Bergmann, Potsdam, GermanyDepartment of Adipocyte Development and Nutrition, German Institute of Human Nutrition (DIfE) Potsdam-Rehbrücke, Nuthetal, GermanyOtto-von-Guericke University Magdeburg, Department of Plastic, Aesthetic and Hand Surgery, Magdeburg, GermanyDepartment of Adipocyte Development and Nutrition, German Institute of Human Nutrition (DIfE) Potsdam-Rehbrücke, Nuthetal, GermanyDepartment of Plastic, Aesthetic and Reconstructive Microsurgery/Hand Surgery, Hospital Ernst von Bergmann, Potsdam, GermanyDepartment of Adipocyte Development and Nutrition, German Institute of Human Nutrition (DIfE) Potsdam-Rehbrücke, Nuthetal, GermanyOtto-von-Guericke University Magdeburg, Department of Plastic, Aesthetic and Hand Surgery, Magdeburg, GermanyDepartment of Adipocyte Development and Nutrition, German Institute of Human Nutrition (DIfE) Potsdam-Rehbrücke, Nuthetal, GermanyGerman Center for Diabetes Research (DZD), München, GermanyDepartment of Adipocyte Development and Nutrition, German Institute of Human Nutrition (DIfE) Potsdam-Rehbrücke, Nuthetal, GermanyOtto-von-Guericke University Magdeburg, Department of Plastic, Aesthetic and Hand Surgery, Magdeburg, GermanyDepartment of Adipocyte Development and Nutrition, German Institute of Human Nutrition (DIfE) Potsdam-Rehbrücke, Nuthetal, GermanyGerman Center for Diabetes Research (DZD), München, GermanyInstitute of Nutritional Science, University of Potsdam, Nuthetal, GermanyDepartment of Plastic, Aesthetic and Reconstructive Microsurgery/Hand Surgery, Hospital Ernst von Bergmann, Potsdam, GermanyIntroductionLipedema is a painful subcutaneous adipose tissue (SAT) disease characterized by adipocyte hypertrophy, immune cell recruitment, and fibrosis in the affected areas. These features are thought to contribute to the development and progression of the condition. However, the relationship between lipedema disease stage and the associated adipose tissue changes has not been determined so far.MethodsSAT biopsies of 32 lipedema patients, ranging across the pathological stages I to III, and 14 BMI- and age-matched controls were harvested from lipedema-affected thighs and non-symptomatic lower abdominal regions. Histological and immunohistochemical (IHC) staining and expression analysis of markers for adipogenesis, immunomodulation, and fibrosis were performed on the tissue biopsies.ResultsLipedema patients showed increased adipocyte areas and a stage-dependent shift towards larger cell sizes in the thighs. Lipedema SAT was linked with increased interstitial collagen accumulation in the thighs, but not the lower abdominal region when compared to controls. There was a trend toward progressive SAT fibrosis of the affected thighs with increasing lipedema stage. Elevated gene expression levels of macrophage markers were found for thigh SAT biopsies, but not in the abdominal region. IHC staining of lipedema thigh biopsies confirmed a transiently elevated macrophage polarization towards an M2-like (anti-inflammatory) phenotype.ConclusionsIn summary, lipedema SAT is associated with stage-dependent adipocyte hypertrophy, stage-progressive interstitial fibrosis and elevated proportion of M2-like macrophages. The character of the inflammatory response differs from primary obesity and may possess an essential role in the development of lipedema.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1223264/fulllipedemalipoedemafibrosisadipose tissueinflammationmacrophages
spellingShingle Philipp Kruppa
Philipp Kruppa
Philipp Kruppa
Sabrina Gohlke
Kamila Łapiński
Kamila Łapiński
Kamila Łapiński
Francisco Garcia-Carrizo
Francisco Garcia-Carrizo
George A. Soultoukis
Manfred Infanger
Tim J. Schulz
Tim J. Schulz
Tim J. Schulz
Mojtaba Ghods
Lipedema stage affects adipocyte hypertrophy, subcutaneous adipose tissue inflammation and interstitial fibrosis
Frontiers in Immunology
lipedema
lipoedema
fibrosis
adipose tissue
inflammation
macrophages
title Lipedema stage affects adipocyte hypertrophy, subcutaneous adipose tissue inflammation and interstitial fibrosis
title_full Lipedema stage affects adipocyte hypertrophy, subcutaneous adipose tissue inflammation and interstitial fibrosis
title_fullStr Lipedema stage affects adipocyte hypertrophy, subcutaneous adipose tissue inflammation and interstitial fibrosis
title_full_unstemmed Lipedema stage affects adipocyte hypertrophy, subcutaneous adipose tissue inflammation and interstitial fibrosis
title_short Lipedema stage affects adipocyte hypertrophy, subcutaneous adipose tissue inflammation and interstitial fibrosis
title_sort lipedema stage affects adipocyte hypertrophy subcutaneous adipose tissue inflammation and interstitial fibrosis
topic lipedema
lipoedema
fibrosis
adipose tissue
inflammation
macrophages
url https://www.frontiersin.org/articles/10.3389/fimmu.2023.1223264/full
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