Adipocytes from lipedema adipose tissue show lipoma-associated nuclear atypia

INTRODUCTION: Lipedema, a painful disease that almost exclusively affects women, leads to an excessive accumulation of subcutaneous adipose tissue, primarily in the extremities. Morphologically, it is characterized by hyperplasia and hypertrophy of adipocytes as well as by inflammation-associated cells and fibrosis. Limited knowledge exists regarding the background of adipocyte pathology. In the present study, we aimed to identify morphological alterations of lipedema adipocytes, which could cause functional implications in lipedema adipose tissue. METHODS: Approximately 3,000 adipocytes from nine lipedema and five control adipose tissue samples, originating from non-obese donors, were analyzed. The ratio of atypical nuclei (Lochkerne) in relation to the total amount of nuclei was assessed and compared between lipedema and non-lipedema samples. RESULTS: Lipedema adipose tissue exhibits a significantly higher proportion of Lochkerne compared to controls (p = 0.001). While 24% of adipocyte nuclei presented as Lochkerne in lipedema samples, only 3% were identifiable in controls. We further show that the process of Lochkern-formation involves the nuclear indentation by small lipid droplets and their subsequent transmigration through the nucleus towards the central lipid content. CONCLUSION: The significantly increased occurrence of lipoma-associated Lochkerne in lipedema adipose tissue compared to controls reveals that, from a morphological point of view, lipedema is a form of lipomatosis.