Despite its increasing incidence and prevalence throughoutWestern countries,
lipedema continues to be a very enigmatic disease, often misunderstood or misdiagnosed by the medical
community and with an intrinsic pathology that is difficult to trace. The nature of lipedemic tissue
is one of hypertrophic adipocytes and poor tissue turnover. So far, there are no identified pathways
responsible, and little is known about the cell populations of lipedemic fat. Methods: Adipose tissue
samples were collected from affected areas of both lipedema and healthy participants. For single-cell
RNA sequencing analysis, the samples were dissociated into single-cell suspensions using enzymatic
digestion and then encapsulated into nanoliter-sized droplets containing barcoded beads. Within each
droplet, cellular mRNA was converted into complementary DNA. Complementary DNA molecules
were then amplified for downstream analysis. Results: The single-cell RNA-sequencing analysis revealed
three distinct adipocyte populations at play in lipedema. These populations have unique gene
signatures which can be characterized as a lipid generating adipocyte, a disease catalyst adipocyte,
and a lipedemic adipocyte. Conclusions: The single-cell RNA sequencing of lipedemic tissue samples
highlights a triad of distinct adipocyte subpopulations, each characterized by unique gene signatures
and functional roles. The interplay between these adipocyte subtypes offers promising insights into
the complex pathophysiology of lipedema.