Project: Characterizing Mitochondrial Phenotypes in Lipedema Adipose Tissue

Principal Investigator: Karthickeyan Chella Krishnan, PhD
Pharmacology, Physiology, and Neurobiology
Assistant Professor
University of Cincinnati
Cincinnati, OH

Summary

This research investigates mitochondrial maladaptations in Lipedema adipose tissue by focusing on distinct mitochondrial subpopulations. By comparing Lipedema patients to matched controls, the study aims to identify bioenergetic, structural, and genomic alterations that contribute to disease pathophysiology and provide a foundation for targeted diagnostic and therapeutic strategies.

Background

Lipedema is a chronic adipose tissue disorder with unclear molecular mechanisms and limited treatment options. Emerging evidence suggests mitochondrial maladaptations, oxidative stress, and altered metabolism contribute to disease pathology. Mitochondria exist as distinct subpopulations with specialized functions, yet their role in Lipedema remains unexplored. This proposal addresses this gap by characterizing mitochondrial subtypes and their functional alterations in Lipedema adipose tissue compared to matched controls.

Methodology

This is an observational study of adipose tissue samples collected from the thigh depot of women with confirmed Lipedema and age- and BMI-matched controls. Stromal vascular fraction (SVF) cells and mitochondrial subpopulations, including cytoplasmic mitochondria (CM) and peridroplet mitochondria (PDM), will be isolated from adipose tissue. No interventions will be performed; comparisons will be made between Lipedema and control samples.

We will measure mitochondrial function using assays that assess mitochondrial respiration, oxidative stress (ROS), membrane potential, and mitochondrial structure. Advanced techniques, including imaging and protein analysis, will be used to evaluate mitochondrial composition and organization. In addition, mitochondrial DNA will be analyzed to identify genetic and/or genomic changes.

The data will be used to determine whether mitochondrial function and structure differ between Lipedema and control samples and to identify specific mitochondrial features associated with disease.

Expected outcomes

We hypothesize that Lipedema adipose tissue exhibits maladaptive mitochondrial alterations, including changes in bioenergetic function, increased oxidative stress, and altered mitochondrial subpopulation dynamics compared to matched controls. We expect to identify distinct mitochondrial phenotypes and/or genomic alterations associated with Lipedema. These findings will provide mechanistic insight into disease pathology and establish a foundation for future studies targeting mitochondrial maladaptations in Lipedema.

Practical implementations of results

This study will identify mitochondrial features that distinguish Lipedema from healthy adipose tissue, providing a basis for developing objective biomarkers for diagnosis and disease staging. The findings may also inform new therapeutic strategies aimed at improving mitochondrial function. Ultimately, this work could lead to more accurate diagnosis, better disease monitoring, and targeted treatments that improve outcomes and quality of life for individuals with Lipedema.

Our Research Grantees by:   Topic | Recent Projects | Past Projects

LF64_25