Transformative Publications


Research funded by the Lipedema Foundation is being published and presented. We have funded about 20% of the Lipedema work published in recent years. Since our funding program began in 2017, our research investments have moved Lipedema knowledge through evidence presented in the publications listed below. You can also search for research papers using the Legato Lipedema Library.

New to Lipedema? Start with the articles indicated by the 👍.


  1. 👍 Al-Ghadban, S., Cromer, W., Allen, M., Ussery, C., Badowski, M., Harris, D., & Herbst, K. L. (2019). Dilated Blood and Lymphatic Microvessels, Angiogenesis, Increased Macrophages, and Adipocyte Hypertrophy in Lipedema Thigh Skin and Fat Tissue. Journal of Obesity, 2019, 8747461. https://doi.org/10.1155/2019/8747461

    • Major obesity journal report supporting idea that Lipedema is not obesity. Demonstration that adipose and vascular remodeling, consistent with changes in the immune system, occur in Lipedema independent of obesity and in a manner unique to Lipedema.

  2. 👍 Al-Ghadban, S., Diaz, Z. T., Singer, H. J., Mert, K. B., & Bunnell, B. A. (2020). Increase in Leptin and PPAR-γ Gene Expression in Lipedema Adipocytes Differentiated in vitro from Adipose-Derived Stem Cells. Cells, 9(2). https://doi.org/10.3390/cells9020430

    • Adipose stem cells collected after liposuction differ in tendency to differentiate to adipocytes dependent on whether they were collected from the abdomen or thigh.

  3. 👍 Al-Ghadban, S., L. Herbst, K., & A. Bunnell, B. (2019). Lipedema: A Painful Adipose Tissue Disorder. In L. Szablewski (Ed.), Adipose Tissue—An Update. IntechOpen. https://doi.org/10.5772/intechopen.88632

    • Contemporary review of biological factors contributing to Lipedema including hypertrophic adipocytes, inflammatory processes, and extracellular fluids.

  4. Al-Ghadban, S., Pursell, I. A., Diaz, Z. T., Herbst, K. L., & Bunnell, B. A. (2020). 3D Spheroids Derived from Human Lipedema ASCs Demonstrated Similar Adipogenic Differentiation Potential and ECM Remodeling to Non-Lipedema ASCs In Vitro. International Journal of Molecular Sciences, 21(21), 8350. https://doi.org/10.3390/ijms21218350

    • Elaborates development of an earlier adipose stem cell model of Lipedema to question earlier publications documenting difference in cell shape, but replicating observations of the tendency of Lipedema derived ASCs to differentiate to adipose.

  5. 👍 Al-Ghadban, S., Teeler, M. L., & Bunnell, B. A. (2021). Estrogen as a Contributing Factor to the Development of Lipedema. In Physiology and Disorders of Adipose Tissue. IntechOpen. https://www.intechopen.com/online-first/estrogen-as-a-contributing-factor-to-the-development-of-lipedema

    • Reviews estrogen's long suspected, but poorly documented relationship to Lipedema

  6. Allen, M., Schwartz, M., & Herbst, K. L. (2020). Interstitial Fluid in Lipedema and Control Skin. Women’s Health Reports (New Rochelle, N.Y.), 1(1), 480–487. https://doi.org/10.1089/whr.2020.0086

    • Eighty Lipedema patient study suggesting vascular and collagen anomalies in Lipedema thighs, compared to abdomen and controls. These were correlated with stage and consistent with leakiness of vessels, as well as propensity to develop lymphedema.

  7. Baranwal, G., Creed, H. A., Cromer, W. E., Wang, W., Upchurch, B. D., Smithhart, M. C., Vadlamani, S. S., Clark, M.-C. C., Busbuso, N. C., Blais, S. N., Reyna, A. J., Dongaonkar, R. M., Zawieja, D. C., & Rutkowski, J. M. (2021). Dichotomous effects on lymphatic transport with loss of caveolae in mice. Acta Physiologica (Oxford, England), e13656. https://doi.org/10.1111/apha.13656

  8. 👍 Bauer, A.-T., von Lukowicz, D., Lossagk, K., Hopfner, U., Kirsch, M., Moog, P., Bauer, H., Machens, H.-G., & Schmauss, D. (2019). Adipose Stem Cells from Lipedema and Control Adipose Tissue Respond Differently to Adipogenic Stimulation In Vitro. Plastic and Reconstructive Surgery, 144(3), 623–632. https://doi.org/10.1097/PRS.0000000000005918

    • Using Adipose stem cells from Lipedema patients as a model, suggests that increased proliferation and decreased differentiation may distinguish Lipedema adipose from Non-Lipedema controls.

  9. Bauer, A.-T.; von Lukowicz, D.; Lossagk, K.; Aitzetmueller, M.; Moog, P.; Cerny, M.; Erne, H.; Schmauss, D.; Duscher, D.; Machens, H.-G. New Insights on Lipedema: The Enigmatic Disease of the Peripheral Fat. Plast Reconstr Surg 2019, 144 (6), 1475–1484. https://doi.org/10.1097/PRS.0000000000006280.

    • German online survey summarizing frequent symptoms, comorbidities, and challenges to quality of life faced by women with Lipedema.

  10. 👍 Beltran, K., & Herbst, K. L. (2017). Differentiating Lipedema and Dercum’s disease. International Journal of Obesity (2005), 41(2), 240–245. https://doi.org/10.1038/ijo.2016.205

    • One of the primary clinical papers describing prevalence of hypermobility and metabolic disorders in Lipedema patients

  11. Bouta, E. M., Blatter, C., Ruggieri, T. A., Meijer, E. F., Munn, L. L., Vakoc, B. J., & Padera, T. P. (2018). Lymphatic function measurements influenced by contrast agent volume and body position. JCI Insight, 3(2), 96591. https://doi.org/10.1172/jci.insight.96591

  12. Chakraborty, A., Barajas, S., Lammoglia, G. M., Reyna, A. J., Morley, T. S., Johnson, J. A., Scherer, P. E., & Rutkowski, J. M. (2019). Vascular Endothelial Growth Factor-D (VEGF-D) Overexpression and Lymphatic Expansion in Murine Adipose Tissue Improves Metabolism in Obesity. The American Journal of Pathology, 189(4), 924–939. https://doi.org/10.1016/j.ajpath.2018.12.008

  13. Chakraborty, A., Scogin, C. K., Rizwan, K., Morley, T. S., & Rutkowski, J. M. (2020). Characterizing Lymphangiogenesis and Concurrent Inflammation in Adipose Tissue in Response to VEGF-D. Frontiers in Physiology, 11, 363. https://doi.org/10.3389/fphys.2020.00363

  14. 👍 Chakraborty, A., Upadhya, R., Usman, T. A., Shetty, A. K., & Rutkowski, J. M. (2021). Chronic VEGFR-3 signaling preserves dendritic arborization and sensitization under stress. Brain, Behavior, and Immunity. https://doi.org/10.1016/j.bbi.2021.08.007

    • Animal model study demonstrating that sustained VEGF activity protects neurons, and may make it easier for them to sense and transmit pain signals offering a mechanism relevant to pain in Lipedema.

  15. Crescenzi, R., Donahue, P. M., Braxton, V. G., Scott, A. O., Mahany, H. B., Lants, S. K., & Donahue, M. J. (2018). 3.0 T relaxation time measurements of human lymph nodes in adults with and without lymphatic insufficiency: Implications for magnetic resonance lymphatic imaging. NMR in Biomedicine, 31(12), e4009. https://doi.org/10.1002/nbm.4009

  16. Crescenzi, R.; Donahue, P. M. C.; Garza, M.; Lee, C. A.; Patel, N. J.; Gonzalez, V.; Jones, R. S.; Donahue, M. J.(2021) Elevated Magnetic Resonance Imaging Measures of Adipose Tissue Deposition in Women with Breast Cancer Treatment-Related Lymphedema. Breast Cancer Res Treat 2021. https://doi.org/10.1007/s10549-021-06419-w.

    • Imaging techniques previously used to study Lipedema used to document relationship between adipose and lymphedema following breast cancer treatment

  17. Crescenzi, R., Donahue, P. M. C., Mahany, H., Lants, S. K., & Donahue, M. J. (2020). CEST MRI quantification procedures for breast cancer treatment-related lymphedema therapy evaluation. Magnetic Resonance in Medicine, 83(5), 1760–1773. https://doi.org/10.1002/mrm.28031

  18. 👍 Crescenzi, R., Donahue, P. M. C., Petersen, K. J., Garza, M., Patel, N., Lee, C., Beckman, J. A., & Donahue, M. J. (2020). Upper and Lower Extremity Measurement of Tissue Sodium and Fat Content in Patients with Lipedema. Obesity (Silver Spring, Md.), 28(5), 907–915. https://doi.org/10.1002/oby.22778

    • High impact journal publication. Using a newly established cohort of Lipedema patients, this study replicates previous findings that tissue sodium levels and fat/water ratios in thigh (but not arm) skin differ between Lipedema patients and matched controls in a manner that correlates to pain and Lipedema stage.

  19. Crescenzi, R., Donahue, P. M. C., Weakley, S., Garza, M., Donahue, M. J., & Herbst, K. L. (2019). Lipedema and Dercum’s Disease: A New Application of Bioimpedance. Lymphatic Research and Biology, 17(6), 671–679. https://doi.org/10.1089/lrb.2019.0011

    • Study of 156 women demonstrating ability of low-cost bioimpedance devices to support a Lipedema differential diagnosis

  20. 👍Crescenzi, R., Marton, A., Donahue, P. M. C., Mahany, H. B., Lants, S. K., Wang, P., Beckman, J. A., Donahue, M. J., & Titze, J. (2018). Tissue Sodium Content is Elevated in the Skin and Subcutaneous Adipose Tissue in Women with Lipedema. Obesity (Silver Spring, Md.), 26(2), 310–317. https://doi.org/10.1002/oby.22090

    • Initial report that sodium levels in skin and subcutaneous adipose tissue objectively measured near the calf were elevated in women with Lipedema along with MRI measures of fat-to-water ratios.

  21. Donahue, P. M. C., Crescenzi, R., Du, L., & Donahue, M. J. (2020). Implementation of Single-Tab Electrodes for Bioimpedance Spectroscopy Measures. Lymphatic Research and Biology, 18(3), 277–283. https://doi.org/10.1089/lrb.2019.0035

  22. Donahue, P. M. C., Crescenzi, R., Lee, C., Garza, M., Patel, N. J., Petersen, K. J., & Donahue, M. J. (2020). Magnetic resonance imaging and bioimpedance evaluation of lymphatic abnormalities in patients with breast cancer treatment-related lymphedema. Breast Cancer Research and Treatment, 183(1), 83–94. https://doi.org/10.1007/s10549-020-05765-5

  23. 👍Donahue, P. M. C., Crescenzi, R., Petersen, K. J., Garza, M., Patel, N., Lee, C., Chen, S.-C., & Donahue, M. J. (2021). Physical Therapy in Women with Early Stage Lipedema: Potential Impact of Multimodal Manual Therapy, Compression, Exercise, and Education Interventions. Lymphatic Research and Biology. https://doi.org/10.1089/lrb.2021.0039

    • Pilot study hinting at positive outcome of physical therapy in Lipedema and lymphedema patients using Quality of Life and tissue sodium imaging

  24. Donahue, P. M. C., Crescenzi, R., Scott, A. O., Braxton, V., Desai, A., Smith, S. A., Jordi, J., Meszoely, I. M., Grau, A. M., Kauffmann, R. M., Sweeting, R. S., Spotanski, K., Ridner, S. H., & Donahue, M. J. (2017). Bilateral Changes in Deep Tissue Environment After Manual Lymphatic Drainage in Patients with Breast Cancer Treatment-Related Lymphedema. Lymphatic Research and Biology, 15(1), 45–56. https://doi.org/10.1089/lrb.2016.0020

  25. 👍 Felmerer, G., Stylianaki, A., Hägerling, R., Wang, A., Ströbel, P., Hollmén, M., Lindenblatt, N., & Gousopoulos, E. (2020). Adipose Tissue Hypertrophy, An Aberrant Biochemical Profile and Distinct Gene Expression in Lipedema. The Journal of Surgical Research, 253, 294–303. https://doi.org/10.1016/j.jss.2020.03.055

    • Based on differences in expressed genes, immune cell recruitment, and tissue changes - this report concludes Lipedema to be uniquely different from either obesity or lymphedema.

  26. 👍 Felmerer, G., Stylianaki, A., Hollmén, M., Ströbel, P., Stepniewski, A., Wang, A., Frueh, F. S., Kim, B.-S., Giovanoli, P., Lindenblatt, N., & Gousopoulos, E. (2020). Increased levels of VEGF-C and macrophage infiltration in Lipedema patients without changes in lymphatic vascular morphology. Scientific Reports, 10(1), 10947. https://doi.org/10.1038/s41598-020-67987-3

    • Biopsies from Lipedema and matched controls were reported to suggest Lipedema is characterized by biochemical, but not structural, changes to lymphatics and recruitment of immune cells to the affected tissues

  27. Grigoriadis, D., Sackey, E., Riches, K., Zanten, M. van, Brice, G., England, R., Mills, M., Dobbins, S. E., Lipoedema Consortium, G. E. R. C., Jeffery, S., Dong, L., Savage, D. B., Mortimer, P. S., Keeley, V., Pittman, A., Gordon, K., & Ostergaard, P. (2021). [Preprint] Investigation of clinical characteristics and genome associations in the ‘UK Lipoedema’ cohort (p. 2021.06.15.21258988). https://doi.org/10.1101/2021.06.15.21258988

  28. Gupta, D. K., Crescenzi, R., & Aday, A. W. (2020). Unpreserved Lymphatic Reserve in Heart Failure With Preserved Ejection Fraction∗. Journal of the American College of Cardiology, 76(24), 2830–2833. https://doi.org/10.1016/j.jacc.2020.10.028

  29. Herbst, K. L. (2020). Insights on the Pathophysiology, Diagnosis and Treatment of Lipedema. Today’s Wound Clinic. https://www.todayswoundclinic.com/articles/insights-pathophysiology-diagnosis-and-treatment-lipedema

  30. 👍 Herbst, K. L., Ussery, C., & Eekema, A. (2017). Pilot study: Whole body manual subcutaneous adipose tissue (SAT) therapy improved pain and SAT structure in women with Lipedema. Hormone Molecular Biology and Clinical Investigation, 33(2). https://doi.org/10.1515/hmbci-2017-0035

    • Small pilot study of deep subcutaneous adipose tissue therapy, reporting benefits to leg function, pain, and leg volume.

  31. 👍 Ibarra, M., Eekema, A., Ussery, C., Neuhardt, D., Garby, K., & Herbst, K. L. (2018). Subcutaneous adipose tissue therapy reduces fat by dual X-ray absorptiometry scan and improves tissue structure by ultrasound in women with lipoedema and Dercum disease. Clinical Obesity, 8(6), 398–406. https://doi.org/10.1111/cob.12281

    • Follow-up study Therapeutic test in six women suggesting reductions in weight and leg volume following Subcutaneous Adipose Therapy when objectively imaged by DXA scanning after 24 sessions.

  32. Jaldin-Fincati, J. R., Pereira, R. V. S., Bilan, P. J., & Klip, A. (2018). Insulin uptake and action in microvascular endothelial cells of lymphatic and blood origin. American Journal of Physiology. Endocrinology and Metabolism, 315(2), E204–E217. https://doi.org/10.1152/ajpendo.00008.2018

  33. Joffin, N., Paschoal, V. A., Gliniak, C. M., Crewe, C., Elnwasany, A., Szweda, L. I., Zhang, Q., Hepler, C., Kusminski, C. M., Gordillo, R., Oh, D. Y., Gupta, R. K., & Scherer, P. E. (2021). Mitochondrial metabolism is a key regulator of the fibro-inflammatory and adipogenic stromal subpopulations in white adipose tissue. Cell Stem Cell. https://doi.org/10.1016/j.stem.2021.01.002

  34. 👍Katzer, K., Hill, J. L., McIver, K. B., & Foster, M. T. (2021). Lipedema and the Potential Role of Estrogen in Excessive Adipose Tissue Accumulation. International Journal of Molecular Sciences, 22(21), 11720. https://doi.org/10.3390/ijms222111720

    • This review postulates how hormonal changes, long thought to influence development of Lipedema, might exert their effects

  35. 👍Kruglikov, I. L., Joffin, N., & Scherer, P. E. (2020). The MMP14-caveolin axis and its potential relevance for lipoedema. Nature Reviews. Endocrinology. https://doi.org/10.1038/s41574-020-0395-z

    • Review article hypothesizing a mechanism to connect the adipose and lymphatic dysfunction, as well as comorbidities, to sex-steroid changes through the activities of tissue remodeling proteins.

  36. Liao, S., Bouta, E. M., Morris, L. M., Jones, D., Jain, R. K., & Padera, T. P. (2019). Inducible Nitric Oxide Synthase and CD11b+Gr1+ Cells Impair Lymphatic Contraction of Tumor-Draining Lymphatic Vessels. Lymphatic Research and Biology, 17(3), 294–300. https://doi.org/10.1089/lrb.2018.0013

  37. McKnight, C. D., Trujillo, P., Lopez, A. M., Petersen, K., Considine, C., Lin, Y.-C., Yan, Y., Kang, H., Donahue, M. J., & Claassen, D. O. (2021). Diffusion along perivascular spaces reveals evidence supportive of glymphatic function impairment in Parkinson disease. Parkinsonism & Related Disorders. https://doi.org/10.1016/j.parkreldis.2021.06.004

  38. Muley, A.; Kim Uh, M.; Salazar-De Simone, G.; Swaminathan, B.; James, J. M.; Murtomaki, A.; Youn, S. W.; McCarron, J. D.; Kitajewski, C.; Gnarra Buethe, M.; Riitano, G.; Mukouyama, Y.-S.; Kitajewski, J.; Shawber, C. J. (2021) Unique Functions for Notch4 in Murine Embryonic Lymphangiogenesis. Angiogenesis. https://doi.org/10.1007/s10456-021-09822-5.

  39. 👍 Petersen, K. J., Garza, M., Donahue, P. M. C., Harkins, K. D., Marton, A., Titze, J., Donahue, M. J., & Crescenzi, R. (2020). Neuroimaging of Cerebral Blood Flow and Sodium in Women with Lipedema. Obesity (Silver Spring, Md.), 28(7), 1292–1300. https://doi.org/10.1002/oby.22837

    • MRI techniques used to suggest that neural symptoms of Lipedema including pain and fatigue are not likely to be due to structural changes in the brain. Mild changes in cerebral blood flow were consistent with other chronic pain conditions.

  40. Stanley, T. L., Leong, A., & Pober, B. R. (2021). Growth, body composition, and endocrine issues in Williams syndrome. Current Opinion in Endocrinology, Diabetes, and Obesity, 28(1), 64–74. https://doi.org/10.1097/MED.0000000000000588

    • Establishes Williams syndrome as a possible gender-independent clinical model of Lipedema with a known genetic origin.

  41. 👍Torre, Y. S.-D. la, Wadeea, R., Rosas, V., & Herbst, K. L. (2018). Lipedema: Friend and foe. Hormone Molecular Biology and Clinical Investigation, 33(1). https://doi.org/10.1515/hmbci-2017-0076

    • Chart review reporting primary evidence supporting long held beliefs that Lipedema is associated with reduced risk of metabolic disease and that symptoms of Lipedema are resistant to diet and exercise.

  42. 👍 Wolf, S., Deuel, J. W., Hollmén, M., Felmerer, G., Kim, B.-S., Vasella, M., Grünherz, L., Giovanoli, P., Lindenblatt, N., & Gousopoulos, E. (2021). A Distinct Cytokine Profile and Stromal Vascular Fraction Metabolic Status without Significant Changes in the Lipid Composition Characterizes Lipedema. International Journal of Molecular Sciences, 22(7), 3313. https://doi.org/10.3390/ijms22073313

    • In a biochemical analysis of lipoaspirates, this report challenges the notion that aberrent lipid profiles can define the condition. The report supports observations of distinct structural changes to the tissue, and characteristic immune recruitment. It further identifies cytokine changes that may change metabolic properties of stromal vascular fractions.

  43. Wong, B. W., Wang, X., Zecchin, A., Thienpont, B., Cornelissen, I., Kalucka, J., García-Caballero, M., Missiaen, R., Huang, H., Brüning, U., Blacher, S., Vinckier, S., Goveia, J., Knobloch, M., Zhao, H., Dierkes, C., Shi, C., Hägerling, R., Moral-Dardé, V., Carmeliet, P. (2017). The role of fatty acid β-oxidation in lymphangiogenesis. Nature, 542(7639), 49–54. https://doi.org/10.1038/nature21028

  44. Yazdani, S., Jaldin‐Fincati, J. R., Pereira, R. V. S., & Klip, A. (2019). Endothelial cell barriers: Transport of molecules between blood and tissues. Traffic, 20(6), 390–403. https://doi.org/10.1111/tra.12645