Lipedema: The Use of Cultured Adipocytes for Identification of Diagnostic Markers

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.

Automated summary

In this study, the adipogenic potential of lipedema and nonlipedema adipose tissue-derived stromal/stem cells were compared. The expression of adipogenic genes was found to be upregulated in adipocytes from nonobese lipedema donors. Furthermore, a reduced adiponectin/leptin ratio and increased occurrence of myofibroblast-like cells were observed in adipocytes from obese lipedema donors.