Lipedema stage affects adipocyte hypertrophy, subcutaneous adipose tissue inflammation and interstitial fibrosis

Abstract

IntroductionLipedema is a painful subcutaneous adipose tissue (SAT) disease characterized by adipocyte hypertrophy, immune cell recruitment, and fibrosis in the affected areas. These features are thought to contribute to the development and progression of the condition. However, the relationship between lipedema disease stage and the associated adipose tissue changes has not been determined so far.MethodsSAT biopsies of 32 lipedema patients, ranging across the pathological stages I to III, and 14 BMI- and age-matched controls were harvested from lipedema-affected thighs and non-symptomatic lower abdominal regions. Histological and immunohistochemical (IHC) staining and expression analysis of markers for adipogenesis, immunomodulation, and fibrosis were performed on the tissue biopsies.ResultsLipedema patients showed increased adipocyte areas and a stage-dependent shift towards larger cell sizes in the thighs. Lipedema SAT was linked with increased interstitial collagen accumulation in the thighs, but not the lower abdominal region when compared to controls. There was a trend toward progressive SAT fibrosis of the affected thighs with increasing lipedema stage. Elevated gene expression levels of macrophage markers were found for thigh SAT biopsies, but not in the abdominal region. IHC staining of lipedema thigh biopsies confirmed a transiently elevated macrophage polarization towards an M2-like (anti-inflammatory) phenotype.ConclusionsIn summary, lipedema SAT is associated with stage-dependent adipocyte hypertrophy, stage-progressive interstitial fibrosis and elevated proportion of M2-like macrophages. The character of the inflammatory response differs from primary obesity and may possess an essential role in the development of lipedema.

Non-obese lipedema patients show a distinctly altered quantitative sensory testing profile with high diagnostic potential

“…Thus, systemic inflammation 34 and hormones 45 may be excluded as core sensitization components. But local inflammation 29,52 also appears unlikely because this should result also in mechanical or thermal hyperalgesia, which we did not detect. Furthermore, amassing of tissue may not cause pain because it should dampen pressure transmission and reduce sensitivity.…”

“…18 But increased pressure transmission and pain may result from a more rigid tissue by, eg, increased extracellular matrix protein underlying a fibrotic phenotype, often attributed to lipedema patients. 29,45 Also, local modality-specific regulation by, eg, secreted proteins, 51 may be an attractive hypothesis and is currently investigated in our laboratory. Thus, despite narrowing the hypotheses, the underlying reason for lipedema pain still remains purely speculative.…”