Project: Identifying Lipedema drivers through secretomic and surfaceome profiling of Lipidemic adipose tissue

Principal Investigator: Peter Jackson
Professor
Departments of Microbiology & Immunology and Pathology
Stanford University School of Medicine
Stanford, CA

Summary

This research explores how signals released by blood vessel cells may contribute to abnormal fat tissue growth in Lipedema. By comparing tissue and cells from people with and without Lipedema, we aim to identify proteins that alter fat cell development and could become targets for future treatments.

Background

Vascular abnormalities have been reported in Lipedema, but how blood vessel cells communicate with nearby fat precursor cells remains poorly understood. Our preliminary laboratory studies show that vascular cells release secreted factors that can either promote or inhibit the maturation of fat cells from progenitors to limit adipogenesis and concurrent growth of new vasculature.  Our project asks whether changes in these secreted factors, or for how fat precursor cells respond to them, contribute to Lipedema.

Methodology

This exploratory laboratory study will compare fat tissue collected during liposuction from patients with Lipedema and controls without Lipedema, prioritizing thigh samples matched for age and body mass index. We will study human fat precursor cells and cells lining blood vessels. First, we will expose fat precursor cells to secreted factors released by vascular endothelial cells and measure fat cell development and fatty acid uptake, comparing responses between Lipedema and control cells. Second, we will label proteins released by blood vessel cells to identify which attach to fat precursor cell surfaces. Third, we will use mass spectrometry, a method for identifying and measuring proteins, to compare proteins in fluid surrounding fat tissue cells. Together, these experiments will identify altered signals and prioritize candidates for further testing. Treatments will be applied only to cells in the laboratory, not to participants.

Expected outcomes

We hypothesize that altered signals from blood vessel cells, together with changes in how fat precursor cells receive or respond to these signals, contribute to abnormal fat tissue expansion in Lipedema. We expect to identify proteins whose abundance, attachment to cell surfaces, or effects on fat cell development differ between lipedema and control samples. These findings will provide a focused set of candidates for further validation.

Practical implementations of results

Our results are targeted to reveal biological mechanisms underlying Lipedema and guide future methods for treatment. We may identify efficacious targets to block or protective signals to restore. This pilot study will also establish methods for analyzing patient tissue and generate the preliminary data needed to design larger studies. Although an early discovery effort, we plan to transition to testing candidate secreted factor therapeutics towards developing new prototypes for Lipedema therapeutics.

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