Project: Dysfunctional Gap Junction Communication Between Endothelium and Adipocytes in Lipedema

Principal Investigator: Brant Isakson, PhD
University of Virginia School of Medicine
Robert M. Berne Cardiovascular Research Center,
Charlottesville, VA

Summary

This research will explore how blood vessels “talk” to the adipocytes in Lipedema patients. Structures termed gap junctions link cells together to allow rapid communication from one cell to another. This is important so that cells in a tissue are aware of external stimuli or cues. We hypothesize that in Lipedema patients, there is a problem with this form of cellular communication that can lead to changes in inflammation or adipocyte proliferation.

Background

There is almost no information on the way in which endothelium and adipocytes may directly interact. This application will explore this possibility using in vitro and in vivo mechanisms to answer that question. Furthermore, the work will identify whether the direct connections are lost in patients with Lipedema, which may drive the etiology of the disease.

Methodology

We approach the project with two models:  an in vitro model and a study of the adipose vasculature and identify how it integrates with adipocytes. The in vitro model will co-culture human adipose endothelium and adipocytes on a polyester membrane. The study of adipose vasculature will primarily focus on electron microscopy ultrastructure to identify the possible connection between endothelium and adipocytes, and if that changes in Lipedema. Controls for this study will be metabolically healthy obese patients. We do not have interventions at this point. The data will be used to provide a new understanding of how Lipedema adipose vasculature may be altered. The next step will be to determine if this can be altered.

Expected outcomes

We hypothesize that in control tissue and in the development of the in vitro co-culture of endothelium and adipocytes, the two cell types will be in contact and have gap junctions that allow for the rapid movement of molecules from one cell to the next. However, we expect that in patients with Lipedema the cell types will not have regular gap junction contact, which may accelerate adipose disfunction.

Practical implementations of results

Whether blood vessels in adipose from patients with Lipedema have a difference in their anatomical structure that would alter the physiological function? Our focus on the possible connections between blood vessels and adipocytes could provide a new avenue of investigation. From a broader perspective, our development of an in vitro co-culture of endothelium and adipocytes may allow rapid testing of pharmacological agents/biomarkers in Lipedema.

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