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Fellow: Javier Jaldin-Fincati, PhD

Institution: The Hospital for Sick Children, Toronto, Canada

Principal Investigator: Amira Klip, PhD

LF Funding History: HRiA/LE&RN/FDRS Postdoctoral Fellowship

Hypothesis: We hypothesize that the products of adipocyte metabolism may affect the normal function of lymphatic microvascular endothelial cells.

Collaborative Opportunities: Javier and Amira look to explore collaborations with leading researchers in adipose cell differentiation and lymphatic system development.

Related News: LE&RN's interview of Javier and his research goals.

Project: Communication Between Adipose and Lymphatic Microvascular Endothelial Cells

We hypothesize that products of adipocyte metabolism may affect the normal function of lymphatic microvascular endothelial cells (L-MEC), contributing to lipedema. We think that if lymphatic capillaries do not drain 'toxic materials' out of adipose tissue, such as fatty acids, an inflammatory state is generated. If we add to this an insufficient removal of excess insulin, a vicious cycle may ensue of insulin resistance in fat cells and inflammation in the tissue that will further damage lymphatic capillaries.

In this context, it is essential to investigate the effect of increased levels of insulin and fatty acids on the metabolism and viability of L-MEC. To address this, we will use L-MEC from human dermal tissue and cultivate them under normal and pathological levels of adipocyte metabolites. This will lead to a better understanding of how these cells respond to healthy and sick environments created by adipose tissue. Subsequent work will examine the influence of pro-inflammatory products and cells on the integrity and survival of lymphatic cells in culture.

Human dermal lymphatic microvascular endothelial cells (HDLEC) form monolayers in vitro. HDLEC present a cobblestone appearance as evidenced by scanning electron microscopy (top left). Actin filaments stained using rhodamine phalloidin, show a cortical distribution pattern (red, top right). The expression of von-Willebrand factor (green, bottom left) and vascular endothelial cadherin (VE-Cadherin magenta, bottom right) confirm the endothelial nature of the HDLEC and the formation of adherent junctions between the cells, respectively. Immunofluorescence images were acquired using a spinning disk confocal microscope, Olympus IX81. Images courtesy of Javier Jaldin-Fincati and Amira Klip, The Hospital for Sick Children, Toronto.

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