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Background/Objectives: Lipedema is a chronic adipose tissue disorder characterized by disproportionate fat accumulation, pain, microvascular dysfunction, and low-grade inflammation. Although low-carbohydrate, high-fat (LCHF) dietary approaches are increasingly used in clinical practice, their longer-term associations with vascular, lymphatic, and immunometabolic pathways in lipedema remain insufficiently understood. This preliminary exploratory study evaluated clinical outcomes and circulating mediators during a 7-month LCHF dietary intervention. Methods: Twenty-four women with lipedema (median age: 39 years) underwent a 7-month individualized, calorie-restricted LCHF diet under medical supervision. Outcomes included body mass index (BMI), leg volume, and adipose tissue pain assessed using a visual analogue scale (VAS). Fasting serum samples collected at baseline and follow-up were analyzed for angiogenic, inflammatory, endothelial, and lipid mediators using Luminex assays and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Results: The intervention was associated with significant reductions in BMI, leg volume, and adipose tissue pain (p < 0.001). These changes were accompanied by increased vascular endothelial growth factor A (VEGF-A), vascular endothelial growth factor D (VEGF-D), and angiopoietin-2 (Ang-2), together with decreased pro-inflammatory cytokines and endothelial adhesion molecules. Several endocannabinoid-related lipid mediators, including oleoyl ethanolamide (OEA), arachidonoyl ethanolamide (AEA), and palmitoyl ethanolamide (PEA), also decreased. Baseline OEA and AEA concentrations, as well as reductions in OEA over time, were associated with greater BMI reduction. Change in interleukin-8 (IL-8) showed a nominal association with leg volume reduction, while pain improvement was associated with decreases in P-selectin and VEGF-A and increases in interleukin-13 (IL-13). Conclusions: A 7-month calorie-restricted LCHF dietary intervention in women with lipedema was associated with clinical improvement and changes in circulating vascular, inflammatory, and lipid mediators. These findings reflect systemic changes accompanying the intervention; however, causal relationships and specific mechanisms cannot be established.

Lipedema is a chronic and progressive adipose tissue disorder characterized by disproportionate fat accumulation, microvascular dysfunction, chronic inflammation, and progressive fibrosis. Despite its prevalence and significant impact on quality of life, current therapeutic approaches remain largely symptomatic and fail to address the underlying biological mechanisms of the disease. Emerging evidence suggests that lipedema should be understood as a multifactorial condition involving genetic susceptibility, endothelial alterations, immune dysregulation, and extracellular matrix remodeling. In this context, pharmacological strategies targeting these pathways have gained increasing attention. Metformin, through activation of AMP-activated protein kinase (AMPK), exerts antifibrotic and immunometabolic effects, including inhibition of TGF-β signaling, reduction of extracellular matrix deposition, and modulation of adipose tissue inflammation. In parallel, incretin-based therapies, particularly glucagon-like peptide-1 (GLP-1) receptor agonists and dual GLP-1/GIP agonists such as tirzepatide, have demonstrated pleiotropic effects that extend beyond weight reduction, including improvements in metabolic homeostasis, reduction of systemic inflammation, and enhancement of endothelial function. These therapies appear to act through complementary mechanisms, with metformin primarily targeting tissue remodeling and fibrosis, and incretin-based therapies exerting broader systemic effects on metabolism, inflammation, and vascular integrity. This review proposes a hypothesis-generating mechanistic framework, supporting a shift from weight-centric and symptomatic approaches toward disease-modifying strategies. Although current evidence in lipedema is largely indirect, the convergence of experimental and clinical data provides a strong rationale for further investigation. Future studies should focus on evaluating combined therapeutic approaches and identifying biomarkers that reflect fibrosis, inflammation, and microvascular dysfunction, with the aim of developing targeted and personalized treatments for this complex disorder.

Infragluteal deformities are a challenging complication following liposuction, particularly when injury occurs to the fibrous osteocutaneous bands of the gluteal crease. Various surgical solutions have been proposed, including autologous fat grafting, skin-lifting procedures, and flap reconstructions, yet a consistent, scar-free, and minimally invasive technique remains elusive. In this report, we present a new modified net suture technique, inspired by the hemostatic net used in aesthetic facial surgery, as a promising treatment for post-liposuction infragluteal deformities. After aggressive power-assisted liposuction to detach mispositioned adhesions within the gluteal crease, we apply a transcutaneous continuous-running suture using non-absorbable nylon, fixed along the newly established crease. The suture is laid loosely to preserve skin perfusion, cushioned by an ointment dressing, and supported with external compression. The technique is completed in approximately 15 minutes, with suture removal on postoperative day 4. In our experience, this approach leads to aesthetically satisfactory outcomes, restores gluteal symmetry, and avoids the formation of additional scars. Our technique is simple, cost-effective, and preserves lymphatic and vascular integrity. This manuscript describes our methodology, rationale, and early clinical observations supporting this low-risk intervention.

Lipedema is a chronic, multifactorial disorder characterized by connective tissue dysregulation, in which vascular dysfunction plays a significant role. Lipedema manifests as symmetrical, painful accumulation of adipose tissue, predominantly in the lower body and arms, with progressive pain, tissue heaviness, and soft-tissue changes across disease stages. Emerging evidence from the micro-to macro-scale implicates endothelial dysfunction, aberrant angiogenesis, and vessel fragility in the pathological accumulation of interstitial fluid leading to tissue edema. Vascular changes are compounded with extracellular matrix remodeling in the form of adipose tissue expansion and fibrosis. Immune cell infiltration and chronic inflammation further contribute to tissue stiffening and adipose hypertrophy, highlighting the role of immune-mediated mechanisms in disease progression. The interplay between vascular, lymphatic, connective tissue, and immune dysfunction emerges as a central determinant of lipedema pathophysiology. Understanding these interconnected mechanisms is critical for elucidating the fundamental biology of lipedema, identifying novel biomarkers, and guiding the development of translational interventions and optimized clinical management strategies.

Methods: Skin and subcutaneous adipose tissue (5-μm sections) were collected from one patient (hand, foot, back), fixed in formaldehyde, and stained for inflammatory markers (CD68, CD163) and endothelial cells (CD31). H&E and Masson’s trichrome staining were performed. Images were captured and manually quantified. Results: Cutaneous tissue from the hands and feet demonstrated increased microvascular density (CD31) with thickened walls, perivascular fibrosis, and macrophage infiltration (CD68, CD163). Macrophages were observed along the nerve fibers and outer nerve layers, consistent with localized nerve inflammation alongside vascular remodeling. Conclusion: This study demonstrates concurrent vascular remodeling and nerve-associated inflammation in lipedema adipose tissue of the hand and feet. These findings highlight that pain in lipedema involves both vascular and neurogenic inflammatory mechanisms, extending the understanding of lipedema pathology beyond the lower extremities.

Background Lipoedema is a condition of abnormal accumulation of painful adipose tissue, usually in the lower body of women. The disproportionate subcutaneous adipose tissue may negatively impact health-related quality of life (HRQoL). There are currently no patient reported outcome measures (PROM) specifically designed to assess the HRQoL in individuals with lipoedema. The aim of this study was to compare scores on validated lower limb lymphoedema PROMs between females with lipoedema and lymphoedema. Methods In a private lymphoedema clinic in Australia between 1 October 2021 and 22 August 2023, individuals assigned female at birth, aged 18 years and older who consented to the entry of de-identified data into a research databank and completed the Lymphoedema Quality of Life tool (LYMQOL-leg) and/or Lymphoedema Symptoms Intensity and Distress Survey (LSIDS-L) for the legs were included in this study. Between group analysis was conducted on 151 participants who were either diagnosed with lipoedema (N = 90) or bilateral leg lymphoedema (N = 61). Participants with both conditions were excluded. Results Participants with lipoedema reported significantly higher burden scores for symptoms (p = 0.003), appearance (p = 0.003) and mood (p = 0.011) in the LYMQOL-leg survey when compared to participants with bilateral leg lymphoedema. Participants with lipoedema also reported significantly worse LSIDS-L scores for neurological sensation (p = 0.003), biobehavioral (p = 0.016) and resource (p = 0.008) questions compared to participants with lymphoedema. Conclusions This study highlights that although females with lipoedema and lymphoedema experience similar symptoms, their experiences differ in specific outcomes that influence their HRQoL. These findings warrant further investigation into the HRQoL concerns of individuals with lipoedema.

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 3000 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.

ObjectiveTo analyse and compare the prevalence of comorbidities associated with lipedema in Spanish women with that in the general population.MethodsA cross-sectional study was conducted using an anonymous online questionnaire distributed among lipedema patient associations in Spain. Sociodemographic variables, clinical aspects, and comorbidities were collected. These were then compared with data from the 2023 National Health Survey, which represents the general Spanish population. The prevalence of each pathology was compared using odds ratios (OR) with 95% confidence intervals. Age-group contributions were assessed using standardised residuals from expected/observed contingency tables, considering absolute values >1.96 (95% confidence) to be significant.ResultsA total of 1001 responses were obtained, with a mean age of 44.2 years. The most prevalent comorbidities were vitamin D deficiency (63.4%), lower limb venous insufficiency (47.2%), and migraine (43.1%). Compared to the general female population in Spain, patients with lipedema were more likely to suffer from venous insufficiency (OR= 5.05; 95% CI: 4.3-5.8), urinary incontinence (OR= 4.93; 95% CI: 4.1-5.8), migraine (OR= 3.9; 95% CI: 3.4-4.5), thyroid disease (OR= 2.21; 95% CI: 1.8-2.6), and asthma (OR= 2.09; 95% CI: 1.7-2.5). However, the probability of hypertension (OR= 0.38; 95% CI: 0.2-0.4) and diabetes (OR= 0.36; 95% CI: 0.2-0.6) was significantly lower.ConclusionsSpanish women with lipedema have a higher prevalence of certain pathologies that should be considered in their medical care. Understanding these relationships is crucial to improving the detection and treatment of patients.

Background/Objectives: Non-invasive radiofrequency (NIRF) therapy is increasingly used in physical rehabilitation. However, its efficacy across differ...

Lymphedema is a common, debilitating condition that challenges treatment efforts. The primary aim of treatment is to debulk the affected areas, providing relief without further damaging tissues or causing undesirable cosmetic outcomes. Liposuction has become a popular treatment for end-stage extremity lymphedema, yet there is no consensus on the most effective technique. Current practices include a range of methods such as dry, wet, superwet, laser-assisted, water-assisted, and power-assisted liposuction. Dry liposuction has sparked controversy, primarily due to concerns that it might be less gentle, and therefore potentially more harmful, than wet liposuction. Contrary to this, we posit that dry liposuction is a viable, low-risk alternative that minimizes the risk of tissue and lymph vessel damage while providing excellent and durable outcomes. This assertion is supported by current literature. In this video article, we present our systematic, step-by-step approach to performing dry liposuction for end-stage lymphedema, illustrating its efficacy and safety. Our personal experience is that patients experience significant reductions in limb volume and report high satisfaction rates, demonstrating that dry liposuction is both effective and reliable for the long-term management of end-stage lymphedema. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors   www.springer.com/00266.

BACKGROUND/OBJECTIVES: Lipedema is a chronic and progressive adipose tissue disorder characterized by the abnormal accumulation of subcutaneous fat, predominantly in the legs and occasionally in the arms. The symptom that most significantly affects the quality of life is pain. Ultrasound elastography is an imaging technology that allows for measuring tissue stiffness quantitatively. This study aims to evaluate the relationship between accompanying pain in patients with lipedema and tissue elasticity measured using shear-wave elastography (SWE). METHODS: Our study was designed as an observational, analytical and cross-sectional study. The visual analog scale (VAS) was used to assess pain, while the PainDetect questionnaire was utilized to evaluate neuropathic pain. The evaluation of tissue elasticity and fibrosis was conducted using the SWE method. RESULTS: This research assessed thirty-five patients, revealing an average age of 45.2 years and an average body mass index (BMI) of 33.6 kg/m². 60% of the patients had a lipedema diagnosis in their family history. Both age (p < 0.01) and BMI (p < 0.001) values were moderately correlated with all subcutaneous adipose tissue measurements, while no correlation was observed in SWE measurements. Only the level of the thigh in the SWE-Elasticity (SWE-E) values was related to VAS (r = 0.35, p = 0.03). Additionally, PainDetect scores demonstrated significant positive correlations with both SWE-velocity (SWE-V) and SWE-E measurements in the thigh region. Specifically, SWE-V showed moderate correlations with PainDetect scores in the right thigh (r = 0.38, p = 0.02) and left thigh (r = 0.47, p = 0.004), while SWE-E was also significantly correlated in both the right (r = 0.44, p = 0.007) and left thighs (r = 0.44, p = 0.008). CONCLUSIONS: While SWE measurements were not correlated with skin adipose tissue, SWE measurements were correlated with pain and neuropathic pain in patients with lipedema. This finding highlights a potentially important relationship between tissue elasticity and pain, which may warrant further exploration. SWE offers a novel, non-invasive approach to quantifying tissue stiffness, providing valuable insights into tissue alterations in women with lipedema.

Lipedema is a lipodystrophic disease characterized primarily by a disproportionate increase in lower body subcutaneous fat. Although moderate weight loss decreases lower body fat mass in women with obesity and lipedema, it is possible that this decrease is due to a reduction in normal subcutaneous fat, rather than lipedema-affected fat. We evaluated the effect of moderate (11%) diet-induced weight loss on body fat mass and distribution, assessed by dual-energy X-ray absorptiometry and magnetic resonance imaging, in a 56-year-old woman with lipedema who was normal weight (body mass index: 23.9 kg/m2) at baseline. Approximately 85% of the decrease in body weight comprised body fat. The relative reduction in upper body fat (abdominal subcutaneous, arm and trunk fat) was similar to the relative reduction in lower body (total leg fat and thigh subcutaneous fat). Accordingly, weight loss did not change the proportion of total body fat comprising leg fat (44.8% and 45.1% before and after weight loss, respectively) or arm fat (9.1% and 9.6% before and after weight loss, respectively). These data suggest weight loss decreases lipedema-affected adipose tissue and demonstrate the therapeutic effect of weight loss on body composition in women with lipedema even if they are normal weight.