Lymphedema alters lipolytic, lipogenic, immune and angiogenic properties of adipose tissue: a hypothesis-generating study in breast cancer survivors.

Autor:	Koc M; Department of Pathophysiology, Centre for Research On Nutrition, Metabolism and Diabetes, Third Faculty of Medicine, Charles University, Ruská 87, 100 00, Prague 10, Czech Republic., Wald M; Department of Surgery, Second Faculty of Medicine, Charles University and Motol University Hospital, Prague 5, Czech Republic., Varaliová Z; Department of Pathophysiology, Centre for Research On Nutrition, Metabolism and Diabetes, Third Faculty of Medicine, Charles University, Ruská 87, 100 00, Prague 10, Czech Republic., Ondrůjová B; Department of Pathophysiology, Centre for Research On Nutrition, Metabolism and Diabetes, Third Faculty of Medicine, Charles University, Ruská 87, 100 00, Prague 10, Czech Republic., Čížková T; Department of Pathophysiology, Centre for Research On Nutrition, Metabolism and Diabetes, Third Faculty of Medicine, Charles University, Ruská 87, 100 00, Prague 10, Czech Republic., Brychta M; Department of Radiotherapy and Oncology, Kralovske Vinohrady University Hospital, Prague 10, Czech Republic., Kračmerová J; Department of Pathophysiology, Centre for Research On Nutrition, Metabolism and Diabetes, Third Faculty of Medicine, Charles University, Ruská 87, 100 00, Prague 10, Czech Republic., Beranová L; Department of Pathophysiology, Centre for Research On Nutrition, Metabolism and Diabetes, Third Faculty of Medicine, Charles University, Ruská 87, 100 00, Prague 10, Czech Republic., Pala J; Department of Pathophysiology, Centre for Research On Nutrition, Metabolism and Diabetes, Third Faculty of Medicine, Charles University, Ruská 87, 100 00, Prague 10, Czech Republic., Šrámková V; Department of Pathophysiology, Centre for Research On Nutrition, Metabolism and Diabetes, Third Faculty of Medicine, Charles University, Ruská 87, 100 00, Prague 10, Czech Republic.; Franco-Czech Laboratory for Clinical Research on Obesity, Third Faculty of Medicine, Prague 10, Czech Republic., Šiklová M; Department of Pathophysiology, Centre for Research On Nutrition, Metabolism and Diabetes, Third Faculty of Medicine, Charles University, Ruská 87, 100 00, Prague 10, Czech Republic.; Franco-Czech Laboratory for Clinical Research on Obesity, Third Faculty of Medicine, Prague 10, Czech Republic., Gojda J; Franco-Czech Laboratory for Clinical Research on Obesity, Third Faculty of Medicine, Prague 10, Czech Republic.; Second Internal Medicine Department, Kralovske Vinohrady University Hospital, Prague 10, Czech Republic., Rossmeislová L; Department of Pathophysiology, Centre for Research On Nutrition, Metabolism and Diabetes, Third Faculty of Medicine, Charles University, Ruská 87, 100 00, Prague 10, Czech Republic. lenka.rossmeislova@lf3.cuni.cz.; Franco-Czech Laboratory for Clinical Research on Obesity, Third Faculty of Medicine, Prague 10, Czech Republic. lenka.rossmeislova@lf3.cuni.cz.
Jazyk:	angličtina
Zdroj:	Scientific reports [Sci Rep] 2021 Apr 14; Vol. 11 (1), pp. 8171. Date of Electronic Publication: 2021 Apr 14.
DOI:	10.1038/s41598-021-87494-3
Abstrakt:	Later stages of secondary lymphedema are associated with the massive deposition of adipose tissue (AT). The factors driving lymphedema-associated AT (LAT) expansion in humans remain rather elusive. We hypothesized that LAT expansion could be based on alterations of metabolic, adipogenic, immune and/or angiogenic qualities of AT. AT samples were acquired from upper limbs of 11 women with unilateral breast cancer-related lymphedema and 11 healthy women without lymphedema. Additional control group of 11 female breast cancer survivors without lymphedema was used to assess systemic effects of lymphedema. AT was analysed for adipocyte size, lipolysis, angiogenesis, secretion of cytokines, immune and stem cell content and mRNA gene expression. Further, adipose precursors were isolated and tested for their proliferative and adipogenic capacity. The effect of undrained LAT- derived fluid on adipogenesis was also examined. Lymphedema did not have apparent systemic effect on metabolism and cytokine levels, but it was linked with higher lymphocyte numbers and altered levels of several miRNAs in blood. LAT showed higher basal lipolysis, (lymph)angiogenic capacity and secretion of inflammatory cytokines when compared to healthy AT. LAT contained more activated CD4+ T lymphocytes than healthy AT. mRNA levels of (lymph)angiogenic markers were deregulated in LAT and correlated with markers of lipolysis. In vitro, adipose cells derived from LAT did not differ in their proliferative, adipogenic, lipogenic and lipolytic potential from cells derived from healthy AT. Nevertheless, exposition of preadipocytes to LAT-derived fluid improved their adipogenic conversion when compared with the effect of serum. This study presents results of first complex analysis of LAT from upper limb of breast cancer survivors. Identified LAT alterations indicate a possible link between (lymph)angiogenesis and lipolysis. In addition, our in vitro results imply that AT expansion in lymphedema could be driven partially by exposition of adipose precursors to undrained LAT-derived fluid.
Databáze:	MEDLINE
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