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

Abstract 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, im...

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Autores principales:	Michal Koc, Martin Wald, Zuzana Varaliová, Barbora Ondrůjová, Terezie Čížková, Milan Brychta, Jana Kračmerová, Lenka Beranová, Jan Pala, Veronika Šrámková, Michaela Šiklová, Jan Gojda, Lenka Rossmeislová
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2fcad79e438d492d9b8804e178ffb481
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spelling	oai:doaj.org-article:2fcad79e438d492d9b8804e178ffb4812021-12-02T14:27:59ZLymphedema alters lipolytic, lipogenic, immune and angiogenic properties of adipose tissue: a hypothesis-generating study in breast cancer survivors10.1038/s41598-021-87494-32045-2322https://doaj.org/article/2fcad79e438d492d9b8804e178ffb4812021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-87494-3https://doaj.org/toc/2045-2322Abstract 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.Michal KocMartin WaldZuzana VaraliováBarbora OndrůjováTerezie ČížkováMilan BrychtaJana KračmerováLenka BeranováJan PalaVeronika ŠrámkováMichaela ŠiklováJan GojdaLenka RossmeislováNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-17 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Michal Koc Martin Wald Zuzana Varaliová Barbora Ondrůjová Terezie Čížková Milan Brychta Jana Kračmerová Lenka Beranová Jan Pala Veronika Šrámková Michaela Šiklová Jan Gojda Lenka Rossmeislová Lymphedema alters lipolytic, lipogenic, immune and angiogenic properties of adipose tissue: a hypothesis-generating study in breast cancer survivors
description	Abstract 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.
format	article
author	Michal Koc Martin Wald Zuzana Varaliová Barbora Ondrůjová Terezie Čížková Milan Brychta Jana Kračmerová Lenka Beranová Jan Pala Veronika Šrámková Michaela Šiklová Jan Gojda Lenka Rossmeislová
author_facet	Michal Koc Martin Wald Zuzana Varaliová Barbora Ondrůjová Terezie Čížková Milan Brychta Jana Kračmerová Lenka Beranová Jan Pala Veronika Šrámková Michaela Šiklová Jan Gojda Lenka Rossmeislová
author_sort	Michal Koc
title	Lymphedema alters lipolytic, lipogenic, immune and angiogenic properties of adipose tissue: a hypothesis-generating study in breast cancer survivors
title_short	Lymphedema alters lipolytic, lipogenic, immune and angiogenic properties of adipose tissue: a hypothesis-generating study in breast cancer survivors
title_full	Lymphedema alters lipolytic, lipogenic, immune and angiogenic properties of adipose tissue: a hypothesis-generating study in breast cancer survivors
title_fullStr	Lymphedema alters lipolytic, lipogenic, immune and angiogenic properties of adipose tissue: a hypothesis-generating study in breast cancer survivors
title_full_unstemmed	Lymphedema alters lipolytic, lipogenic, immune and angiogenic properties of adipose tissue: a hypothesis-generating study in breast cancer survivors
title_sort	lymphedema alters lipolytic, lipogenic, immune and angiogenic properties of adipose tissue: a hypothesis-generating study in breast cancer survivors
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/2fcad79e438d492d9b8804e178ffb481
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Lymphedema alters lipolytic, lipogenic, immune and angiogenic properties of adipose tissue: a hypothesis-generating study in breast cancer survivors

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