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  • Al-Ghadban, S., Evancio, J. V., Alfiscar, P. E. F., & Herbst, K. L. (2025). New Characterization of Lipedema Stages: Focus on Pain, Water, Fat and Skeletal Muscle. Life, 15(9), 1397. https://doi.org/10.3390/life15091397

    Lipedema is a chronic, progressive adipose connective tissue disorder characterized by symmetrical, disproportionate fat accumulation, typically affecting the lower extremities and arms, accompanied by pain, swelling, and a sensation of heaviness. This study introduces intermediate Stages 1.5 and 2.5 to the established lipedema classification (Stages 1, 2 and 3), and other affected areas, based on physical examination, a questionnaire, and photographic documentation. Bioelectrical Impedance Spectroscopy (BIS) was employed to quantify total body water (TBW) across stages. A significant and linear increase in BMI was observed from Stage 1 to 3, correlating with increased reported pain and heaviness in the thighs, calves, and upper arms. Systemic symptoms of brain fog, debilitating fatigue, and hypothermia were significantly prevalent. TBW demonstrated a significant, stage-dependent increase in the lower extremities. Adipose tissue accumulation over the knees and feet significantly increased with lipedema stage. In contrast, shin involvement was evident in early stages and remained consistently elevated throughout later stages. Skeletal Muscle Mass (SMM) exhibited a significant increase across lipedema stages, positively correlating with fat mass (FM) in Stage 3. This study elucidates previously underrecognized clinical features and distribution patterns of lipedema, offering a refined staging system to improve understanding of its progression and burden.

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  • Straub, L. G., Funcke, J.-B., Joffin, N., Joung, C., Al-Ghadban, S., Zhao, S., Zhu, Q., Kruglikov, I. L., Zhu, Y., Langlais, P. R., Gordillo, R., Herbst, K. L., & Scherer, P. E. (2025). Defining lipedema’s molecular hallmarks by multi-omics approach for disease prediction in women. Metabolism, 156191. https://doi.org/10.1016/j.metabol.2025.156191

    Lipedema is a chronic disease in females characterized by pathologic subcutaneous adipose tissue expansion and hitherto remains without druggable targets. In this observational study, we investigated the molecular hallmarks of lipedema using an unbiased multi-omics approach. We found adipokine dysregulation in lipedema patients participating in a cross-sectional clinical study (ClinicalTrial.gov, NCT02838277), pointing towards the adipocyte as a key player. Analyses of newly generated transcriptomic (SRA, PRJNA940039) and proteomic (ProteomeXchange, PXD058489) datasets of early- and late-stage lipedema samples revealed a local downregulation of factors involved in inflammation. Concomitantly, factors involved in cellular respiration, oxidative phosphorylation, as well as in mitochondrial organization were upregulated. Measuring a cytokine and chemokine panel in the serum of non-menopausal women, we observed little systemic changes in inflammatory markers, but a trend towards increased VEGF. Metabolomic and lipidomic analyses highlighted altered circulating glutamic acid, glutathione, and sphingolipid levels, suggesting a broader dysregulation of metabolic and inflammatory processes. We subsequently benchmarked a set of models to accurately predict lipedema using serum factor measurements (sLPM). Our study of the molecular signature of lipedema thus provides not only potential targets for therapeutic intervention, but also candidate markers of disease development and progression.

    View on www.sciencedirect.com
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Last update from database: 10/7/25, 7:34 AM (UTC)