Project: Assessment of gene expression-based molecular biomarkers for lipedema diagnosis, reproducible disease staging, and personalized clinical care

Principal Investigator: Philipp Kruppa, MD
Klinikum Ernst von Bergmann gGmbH
Department of Plastic, Aesthetic and Reconstructive Microsurgery/Hand Surgery
Potsdam, Germany
Co-Principal Investigator: Sabrina Gohlke, PhD
Department of Adipocyte Development and Nutrition (ADE)
German Institute of Human Nutrition Potsdam-Rehbruecke
Potsdam, Germany
Co-Principal Investigator: Mojtaba Ghods, MD, PhD
Klinikum Ernst von Bergmann gGmbH
Department of Plastic, Aesthetic and Reconstructive Microsurgery/Hand Surgery
Potsdam, Germany
Co-Principal Investigator: Tim J. Schulz, PhD
Department of Adipocyte Development and Nutrition (ADE)
German Institute of Human Nutrition Potsdam-Rehbruecke
Potsdam, Germany

Summary

This project aims to address the challenge of correctly diagnosing Lipedema by investigating the role of inflammation and molecular changes in the disease's progression. Through advanced molecular analysis techniques, the study aims to uncover specific pathways and cell populations contributing to Lipedema's characteristics and clinical stages. The ultimate goal is to enhance diagnostic accuracy for Lipedema patients by identifying predictive biomarkers.

Background

Lipedema involves changes in fat cell morphology, fibrotic tissue accumulation, and alterations in immune cells. This is reported to be linked to an early shift in macrophage polarization towards an anti-inflammatory (M2-like) phenotype. The exact molecular mechanisms affecting immune cell functions and the role of inflammation in Lipedema's pathogenesis remain unclear. Furthermore, studies link subcutaneous fat tissue changes and inflammation to disease severity, but a comprehensive analysis of cellular and molecular changes is lacking.

Methodology

The research involves 60 lipedema patients (20 per disease stage), and 20 individuals without Lipedema matched for BMI and age as control group. Tissue samples are collected from the abdominal fat, which is not affected and Lipedema-affected thigh regions. Next generation sequencing is used to measure gene expression patterns. Enzymatic activities related to lipid processing are evaluated through mass spectrometric semi-quantitative analysis of specific lipid species, the fatty acids, that correspond to the storage fats in the tissue. The cellular composition of the fat biopsies is examined using single cell-based technologies in a subset of 12 Lipedema patients (4 per stage) and matched individuals without Lipedema. The study's strength lies in its comprehensive approach, integrating gene expression analysis, cell-type profiling, and assessment of metabolism. By correlating these data, the study aims to provide a comprehensive understanding of Lipedema's pathophysiology and progression for optimal diagnosis at different disease stages.

Expected outcomes

We hypothesize that tissue fatty acid composition might serve as a predictive biomarker which correlates to genetic and clinical markers to help improve diagnostic robustness. We anticipate that gene expression of pathway markers could enhance diagnostic tools, particularly focusing on immunomodulation and fibrosis pathways. Single cell-analysis techniques are expected to help uncover cellular heterogeneities to delineate disease staging the development of effective treatment plans. Additionally, we aim to identify distinct metabolic health markers in Lipedema-affected fat depots, offering insights into disease progression.

Practical implementations of results

Despite recent attention, the underlying cause of Lipedema remains elusive. This research project has the potential to extend our fundamental understanding of Lipedema's pathogenesis and its implications for whole-body metabolism and health. It could improve the precision of diagnosis and help identify appropriate staging procedures. Through this study, we aim to introduce novel molecular knowledge into the field, fostering an improved understanding of the disease and potentially advancing treatment approaches for affected individuals.

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