Lipedema is a condition of white adipose tissue (WAT), however it differs from “normal” WAT and obesity-associated WAT.
We need normal WAT for lipid and energy storage; however, it can shift to metabolically unhealth WAT in obesity where the tissue is not only growing due to hyperplasia (new fat cells seen in normal expansion of WAT) but also hypertrophy (cells increase in size). These larger sized fat cells can lead to hypoxia, fibrosis, and disruption of normal energy balance in the cells. These cells become stressed and die off at higher rates leading to immune activation. In obesity, this means high levels of pro-inflammatory M1 macrophages infiltrate the tissue. Other changes take place resulting in systemic consequences including elevated leptin and leptin resistance which can disrupt appetite regulation, low adiponectin resulting in insulin resistance, and elevated inflammatory cytokines causing systemic low-grade inflammation. Free fatty acids, rather than being contained in the WAT, can spill out and find a new home in other organs causing conditions like fatty liver.
Lipedema WAT is similar from obesity WAT in that expansion is due to both hyperplasia and hypertrophy of fat cells which results in hypoxia, fibrosis, and disrupted energy balance. Lipedema WAT is different from obesity WAT in several structural, metabolic, and systemic ways. Structurally, lipedema tissue traps proteoglycans like hyaluronic acid which traps water. This can be beneficial in a skincare routine, but not great for lipedema tissue where in combination with fibrosis results in palpable nodules.[1] Though both obesity and lipedema WAT shows reduced vascularization, only lipedema is associated with the degree of capillary fragility from endothelial cell dysfunction that leads to characteristic easy bruising, pain with pressure, and edema. Also unlike obesity WAT, lipedema is associated with an anti-inflammatory M2 macrophage phenotype which is metabolically protective and may help preserve systemic insulin sensitivity. We also don’t see the same systemic spilling of free fatty acids that we do in obesity. The lipedema WAT is still a functional metabolic sink for storing lipids.
Brown Adipose Tissue
Brown adipose tissue (BAT) gets its color from the high concentration of iron-rich mitochondria found in the tissue. It also has high levels of vascularization and innervations from the sympathetic nervous system. BAT has a net energy expenditure, helps generate heat (thermogenesis), and is associated with lower risk of type 2 diabetes, insulin resistance, fatty liver disease, coronary artery disease, and more.
Increasing BAT in normal WAT
The primary signals to stimulate brown adipose tissue include cold exposure, sympathetic nervous stimulation, exercise, and sleep, and some dietary compounds like capsaicin,[2] EGCG from green tea, resveratrol, and quercetin[3] have been shown to have an effect. Cold exposure doesn’t have to be as extreme as a cold plunge. One study published in The Journal of Clinical Investigation showed spending a couple of hours in a cooler room (66 F) increases BAT volume and glucose clearance.[4]
Normal WAT can undergo “beiging” but certain types, like normal subcutaneous WAT, have a much higher propensity to beige than obesity or lipedema WAT. Lipedema WAT is subcutaneous WAT and has the genetic machinery required to transform into brown fat, however there are clearly obstacles preventing this transition or the fat would be more responsive to diet and exercise. Studies point to fluid and fibrotic buffers that insulate the fat from some of the stressors that would normally trigger browning as well as suppression by chronic immune activation leading to thermogenic resistance. [5-7]
Treatment interventions are under investigation for their potential role in disrupting these physical, hormonal, and signaling barriers including GLP-1/GIP receptor agonists that may help the tissue respond more like normal WAT. [8]
Lipedema doesn’t happen in a vacuum of course and people with lipedema can still have metabolic benefits from optimizing sleep, exercise, and eating a diet rich in polyphenols.
Sources
- Lipedema Foundation Research Consortium. (2025). Lipedema and adipose tissue: Current understanding, controversies, and future directions. Reviews in Endocrine and Metabolic Disorders. Advance online publication. https://doi.org/10.1007/s11154-025-12631-4 (PMCID: PMC12631410)
- Yoneshiro, T., Aita, S., Matsushita, M., Kayahara, T., Kameya, T., Kawai, Y., Iwanaga, T., & Saito, M. (2012). Nonpungent capsaicin analogs (capsinoids) increase energy expenditure through the activation of brown adipose tissue in humans. The American Journal of Clinical Nutrition, 95(4), 845–850. https://doi.org/10.3945/ajcn.111.018606
- Zhang, S., Chang, J., & Zhang, J. (2021). Natural polyphenols as candidates for the browning of white adipose tissue and the activation of brown adipose tissue. Frontiers in Endocrinology, 12, Article 798403. https://doi.org/10.3389/fendo.2021.798403
- van der Lans, A. A., Hoeks, J., Brans, B., Vijgen, G. H., Visser, M. G., Vosselman, M. J., Hansen, J., Jardon, A. M., Schaart, G., Schrauwen, P., & van Marken Lichtenbelt, W. D. (2013). Cold acclimation recruits human brown fat and increases nonshivering thermogenesis. The Journal of Clinical Investigation, 123(8), 3395–3403. https://doi.org/10.1172/JCI68060
- Priglinger, E., Haerteis, S., & Schiltz, D. (2022). Adipose tissue remodeling in lipedema: Insights into extracellular matrix fibrosclerosis and stem cell dysregulation. Journal of Clinical Investigation, 132(8), e145887. https://doi.org/10.1172/JCI145887 (Grant ID: LF4221)
- Al-Ghadban, S., & Cromer, W. E. (2024). Vascular and nerve-associated inflammation in lipedema hand and foot tissue: A case report & pathological review. Hypodermis & Adipose Histopathology, 6(1), 112–125.
- Hossain, M. A. (2026). Targeting mitochondrial dysfunction in lipedema: A pharmacological approach to enhance metabolic flexibility [Abstract/Presentation]. Scholarly Commons, University of the Pacific. https://scholarlycommons.pacific.edu/rcs/2026/events/117/
- Beltran, K. J., & Herbst, K. L. (2025). Tirzepatide as a potential disease-modifying therapy in lipedema: A narrative review on bridging metabolism, inflammation, and fibrosis. International Journal of Molecular Sciences, 26(4), 1802. https://doi.org/10.3390/ijms26041802 (PMCID: PMC12608556)
