Lipedema: The Use of Cultured Adipocytes for Identification of Diagnostic Markers.
Journal
Plastic and reconstructive surgery
ISSN: 1529-4242
Titre abrégé: Plast Reconstr Surg
Pays: United States
ID NLM: 1306050
Informations de publication
Date de publication:
01 11 2023
01 11 2023
Historique:
medline:
30
10
2023
pubmed:
14
3
2023
entrez:
13
3
2023
Statut:
ppublish
Résumé
Lipedema, diagnosed most often in women, is a progressive disease characterized by the disproportionate and symmetrical distribution of adipose tissue, primarily in the extremities. Although numerous results from in vitro and in vivo studies have been published, many questions regarding the pathology and genetic background of lipedema remain unanswered. In this study, adipose tissue-derived stromal/stem cells were isolated from lipoaspirates derived from nonobese and obese donors with or without lipedema. Growth and morphology, metabolic activity, differentiation potential, and gene expression were evaluated using quantification of lipid accumulation, metabolic activity assay, live-cell imaging, reverse transcription polymerase chain reaction, quantitative polymerase chain reaction, and immunocytochemical staining. The adipogenic potential of lipedema and nonlipedema adipose tissue-derived stromal/stem cells did not rise in parallel with the donors' body mass index and did not differ significantly between groups. However, in vitro differentiated adipocytes from nonobese lipedema donors showed significant upregulation of adipogenic gene expression compared with nonobese controls. All other genes tested were expressed equally in lipedema and nonlipedema adipocytes. The adiponectin/leptin ratio was significantly reduced in adipocytes from obese lipedema donors compared with their nonobese lipedema counterparts. Increased stress fiber-integrated smooth muscle actin was visible in lipedema adipocytes compared with nonlipedema controls and appeared enhanced in adipocytes from obese lipedema donors. Not only lipedema per se but also body mass index of donors affect adipogenic gene expression substantially in vitro. The significantly reduced adiponectin/leptin ratio and the increased occurrence of myofibroblast-like cells in obese lipedema adipocyte cultures underscores the importance of attention to the co-occurrence of lipedema and obesity. These are important findings toward accurate diagnosis of lipedema. Our study highlights not only the difficulty in lipedema diagnostics but also the tremendous need for further studies on lipedema tissue. Although lipedema might seem to be an underestimated field in plastic and reconstructive surgery, the power it holds to provide better treatment to future patients can not be promoted enough.
Sections du résumé
BACKGROUND
Lipedema, diagnosed most often in women, is a progressive disease characterized by the disproportionate and symmetrical distribution of adipose tissue, primarily in the extremities. Although numerous results from in vitro and in vivo studies have been published, many questions regarding the pathology and genetic background of lipedema remain unanswered.
METHODS
In this study, adipose tissue-derived stromal/stem cells were isolated from lipoaspirates derived from nonobese and obese donors with or without lipedema. Growth and morphology, metabolic activity, differentiation potential, and gene expression were evaluated using quantification of lipid accumulation, metabolic activity assay, live-cell imaging, reverse transcription polymerase chain reaction, quantitative polymerase chain reaction, and immunocytochemical staining.
RESULTS
The adipogenic potential of lipedema and nonlipedema adipose tissue-derived stromal/stem cells did not rise in parallel with the donors' body mass index and did not differ significantly between groups. However, in vitro differentiated adipocytes from nonobese lipedema donors showed significant upregulation of adipogenic gene expression compared with nonobese controls. All other genes tested were expressed equally in lipedema and nonlipedema adipocytes. The adiponectin/leptin ratio was significantly reduced in adipocytes from obese lipedema donors compared with their nonobese lipedema counterparts. Increased stress fiber-integrated smooth muscle actin was visible in lipedema adipocytes compared with nonlipedema controls and appeared enhanced in adipocytes from obese lipedema donors.
CONCLUSIONS
Not only lipedema per se but also body mass index of donors affect adipogenic gene expression substantially in vitro. The significantly reduced adiponectin/leptin ratio and the increased occurrence of myofibroblast-like cells in obese lipedema adipocyte cultures underscores the importance of attention to the co-occurrence of lipedema and obesity. These are important findings toward accurate diagnosis of lipedema.
CLINICAL RELEVANCE STATEMENT
Our study highlights not only the difficulty in lipedema diagnostics but also the tremendous need for further studies on lipedema tissue. Although lipedema might seem to be an underestimated field in plastic and reconstructive surgery, the power it holds to provide better treatment to future patients can not be promoted enough.
Identifiants
pubmed: 36912938
doi: 10.1097/PRS.0000000000010392
pii: 00006534-202311000-00025
doi:
Substances chimiques
Leptin
0
Adiponectin
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1036-1046Subventions
Organisme : Land Salzburg (AT)
ID : 20204-WISS/240/3-2019
Informations de copyright
Copyright © 2023 by the American Society of Plastic Surgeons.
Références
Buck DW 2nd, Herbst KL. Lipedema: a relatively common disease with extremely common misconceptions. Plast Reconstr Surg Glob Open. 2016;4:e1043.
Fife CE, Maus EA, Carter MJ. Lipedema: a frequently misdiagnosed and misunderstood fatty deposition syndrome. Adv Skin Wound Care. 2010;23:81–92; quiz 93.
Okhovat JP, Alavi A. Lipedema: a review of the literature. Int J Low Extrem Wounds. 2015;14:262–267.
Forner-Cordero I, Szolnoky G, Forner-Cordero A, Kemeny L. Lipedema: an overview of its clinical manifestations, diagnosis and treatment of the disproportional fatty deposition syndrome: systematic review. Clin Obes. 2012;2:86–95.
Herbst KL, Mirkovskaya L, Bharhagava A, Chava Y, Te CHT. Lipedema fat and signs and symptoms of illness, increase with advancing stage. Arch Med. 2015;7:1–8.
Paolacci S, Precone V, Acquaviva F, et al.; GeneOb Project. Genetics of lipedema: new perspectives on genetic research and molecular diagnoses. Eur Rev Med Pharmacol Sci. 2019;23:5581–5594.
Priglinger E, Wurzer C, Steffenhagen C, et al. The adipose tissue-derived stromal vascular fraction cells from lipedema patients: are they different? Cytotherapy. 2017;19:849–860.
Bauer AT, von Lukowicz D, Lossagk K, et al. Adipose stem cells from lipedema and control adipose tissue respond differently to adipogenic stimulation in vitro. Plast Reconstr Surg. 2019;144:623–632.
Al-Ghadban S, Diaz ZT, Singer HJ, Mert KB, Bunnell BA. Increase in leptin and PPAR-γ gene expression in lipedema adipocytes differentiated in vitro from adipose-derived stem cells. Cells. 2020;9:430.
Al-Ghadban S, Pursell IA, Diaz ZT, Herbst KL, Bunnell BA. 3D Spheroids derived from human lipedema ASCs demonstrated similar adipogenic differentiation potential and ECM remodeling to non-lipedema ASCs in vitro. Int J Mol Sci. 2020;21:8350.
Herbst KL. Subcutaneous adipose tissue diseases: Dercum disease, lipedema, familial multiple lipomatosis, and Madelung disease. In Feingold KR, Anawalt B, Boyce A, ., eds. Endotext. South Dartmouth, MA: MDText.com, Inc.; 2000.
Tremp M, Menzi N, Tchang L, di Summa PG, Schaefer DJ, Kalbermatten DF. Adipose-derived stromal cells from lipomas: isolation, characterisation and review of the literature. Pathobiology. 2016;83:258–266.
Caponnetto F, Manini I, Bulfoni M, et al. Human adipose-derived stem cells in Madelung’s disease: morphological and functional characterization. Cells. 2020;10:44.
Al-Ghadban S, Cromer W, Allen M, et al. Dilated blood and lymphatic microvessels, angiogenesis, increased macrophages, and adipocyte hypertrophy in lipedema thigh skin and fat tissue. J Obes. 2019;2019:8747461.
Felmerer G, Stylianaki A, Hägerling R, et al. Adipose tissue hypertrophy: an aberrant biochemical profile and distinct gene expression in lipedema. J Surg Res. 2020;253:294–303.
Wolf S, Deuel JW, Hollmén M, et al. A distinct cytokine profile and stromal vascular fraction metabolic status without significant changes in the lipid composition characterizes lipedema. Int J Mol Sci. 2021;22:3313.
Aksoy H, Karadag AS, Wollina U. Cause and management of lipedema-associated pain. Dermatol Ther. 2021;34:e14364.
Bilancini S, Lucchi M, Tucci S, Eleuteri P. Functional lymphatic alterations in patients suffering from lipedema. Angiology. 1995;46:333–339.
Ma W, Gil HJ, Escobedo N, et al. Platelet factor 4 is a biomarker for lymphatic-promoted disorders. JCI Insight. 2020;5:e135109.
Gould DJ, El-Sabawi B, Goel P, Badash I, Colletti P, Patel KM. Uncovering lymphatic transport abnormalities in patients with primary lipedema. J Reconstr Microsurg. 2020;36:136–141.
Sarantopoulos CN, Banyard DA, Ziegler ME, Sun B, Shaterian A, Widgerow AD. Elucidating the preadipocyte and its role in adipocyte formation: a comprehensive review. Stem Cell Rev. 2018;14:27–42.
Brooks AES, Iminitoff M, Williams E, et al. Ex vivo human adipose tissue derived mesenchymal stromal cells (ASC) are a heterogeneous population that demonstrate rapid culture-induced changes. Front Pharmacol. 2019;10:1695.
van Harmelen V, Skurk T, Röhrig K, et al. Effect of BMI and age on adipose tissue cellularity and differentiation capacity in women. Int J Obes Relat Metab Disord. 2003;27:889–895.
Pachón-Peña G, Serena C, Ejarque M, et al. Obesity determines the immunophenotypic profile and functional characteristics of human mesenchymal stem cells from adipose tissue. Stem Cells Transl Med. 2016;5:464–475.
Frühbeck G, Catalán V, Rodríguez A, et al. Adiponectin-leptin ratio is a functional biomarker of adipose tissue inflammation. Nutrients. 2019;11:454.
Frühbeck G, Catalán V, Rodríguez A, Gómez-Ambrosi J. Adiponectin-leptin ratio: a promising index to estimate adipose tissue dysfunction: relation with obesity-associated cardiometabolic risk. Adipocyte. 2018;7:57–62.
Gao H, Volat F, Sandhow L, et al. CD36 is a marker of human adipocyte progenitors with pronounced adipogenic and triglyceride accumulation potential. Stem Cells. 2017;35:1799–1814.
Li Y, Jin D, Xie W, et al. PPAR-γ and Wnt regulate the differentiation of MSCs into adipocytes and osteoblasts respectively. Curr Stem Cell Res Ther. 2018;13:185–192.
Berger J, Moller DE. The mechanisms of action of PPARs. Annu Rev Med. 2002;53:409–435.
Prentice KJ, Saksi J, Hotamisligil GS. Adipokine FABP4 integrates energy stores and counterregulatory metabolic responses. J Lipid Res. 2019;60:734–740.
Shen JX, Couchet M, Dufau J, et al. 3D adipose tissue culture links the organotypic microenvironment to improved adipogenesis. Adv Sci. 2021;8:2100106.
Oberkofler H, Dallinger G, Liu YM, Hell E, Krempler F, Patsch W. Uncoupling protein gene: quantification of expression levels in adipose tissues of obese and non-obese humans. J Lipid Res. 1997;38:2125–2133.
Eyden B. The myofibroblast: phenotypic characterization as a prerequisite to understanding its functions in translational medicine. J Cell Mol Med. 2008;12:22–37.
Zhao X, Gong P, Lin Y, Wang J, Yang X, Cai X. Characterization of α-smooth muscle actin positive cells during multilineage differentiation of dental pulp stem cells. Cell Prolif. 2012;45:259–265.
Cai X, Lin Y, Hauschka PV, Grottkau BE. Adipose stem cells originate from perivascular cells. Biol Cell. 2011;103:435–447.