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Background: Lipedema is a chronic disorder of subcutaneous adipose tissue characterized by symmetrical fat accumulation in the extremities, pain, and orthostatic edema. Objectives: This study aimed to assess whether high-resolution cutaneous ultrasound can detect measurable tissue-level changes in subcutaneous tissue over six months. Methods: A retrospective, single-center, real-world longitudinal observational cohort study was conducted in 60 women with lipedema followed at three timepoints (baseline, 3 months, 6 months). High-resolution ultrasound (18–20 MHz) measured subcutaneous and dermal thickness at standardized anatomical sites. Results: All primary ultrasound parameters decreased significantly over six months of conservative multicomponent management, which included individualized nutritional counseling and physical activity. Medial proximal thigh subcutaneous thickness declined by 18.7% (48.2 to 39.2 mm; p < 0.001). Edema prevalence fell from 100% to 55.0%. Echogenicity improved significantly between 3 and 6 months, suggesting a delayed structural remodelling effect distinct from early volumetric reduction. Ultrasound reductions were inversely correlated with weight loss, suggesting that ultrasound captures tissue-level information not fully reflected by anthropometric measures alone. Conclusions: Standardized cutaneous high-resolution ultrasound detected consistent tissue-level modifications over six months of routine clinical follow-up, capturing changes beyond anthropometric measures and representing a candidate monitoring tool warranting evaluation in controlled study designs.

Background: Lipedema is a chronic disorder that predominantly affects women and is characterized by abnormal subcutaneous adipose tissue accumulation, pain, and vascular dysfunction. However, reliable circulating biomarkers that reflect disease-specific pathophysiology are still lacking. This study investigated serum markers associated with adipose tissue, inflammation, and angiogenesis to further elucidate the pathophysiology of lipedema. Methods: In this cross-sectional observational study, fasting serum levels of adiponectin, chemerin, lipopolysaccharide-binding protein (LBP), proprotein convertase subtilisin/kexin type 9 (PCSK9), soluble CD163 (sCD163), and soluble CD137 (sCD137)—proteins associated with obesity and inflammation—were measured in 23 premenopausal women with lipedema and 23 age-matched healthy premenopausal controls. Serum endostatin levels, an angiogenesis inhibitor, and insulin-like growth factor binding protein 2 (IGFBP2), a potent proangiogenic factor, were also assessed. Results: Patients with lipedema and obese controls had comparable body mass index, glucose, and serum lipid profiles. No significant differences were observed between groups in circulating levels of adiponectin, chemerin, LBP, PCSK9, sCD163, sCD137 and IGFBP2. In contrast, serum endostatin levels were significantly reduced in patients with lipedema (p = 0.038). Additional analyses demonstrated markedly higher endostatin expression in human subcutaneous adipose tissue than in the liver, suggesting that circulating endostatin levels may be related to adipose tissue mass. However, serum endostatin levels were lower in obese compared with normal-weight women (p < 0.001). Conclusion: Lipedema was not associated with altered circulating levels of adiponectin, chemerin, LBP, PCSK9, sCD163, sCD137 or IGFBP2. Reduced serum endostatin levels support a potential role for vascular dysfunction in the pathophysiology of lipedema.

Objectives: To examine the associations of ultra-processed food (UPF) consumption, dietary inflammatory index (DII), and Mediterranean diet adherence with pain severity, physical quality of life, body composition, and inflammatory markers in women with lipedema. Methods: This cross-sectional study included women diagnosed with lipedema across different disease stages. Dietary intake was assessed using a validated food frequency questionnaire, and foods were classified according to the NOVA system to determine UPF consumption. The dietary inflammatory index was calculated to assess the inflammatory potential of the diet, and Mediterranean diet adherence was evaluated using a standardized scoring system. Anthropometric measurements, body composition parameters, inflammatory markers, pain intensity (VAS), and physical quality of life (SF-12 PCS) were assessed. Multivariable regression analyses were performed to investigate the associations between dietary variables and clinical outcomes. Results: A total of 86 women with lipedema (stage 1: n=36, stage 2: n=33, stage 3: n=17) were included. UPF consumption increased from 28.1% to 41.3% of total energy and DII scores from +1.46 to +3.02 across stages, while Mediterranean diet adherence decreased from 28.2 to 21.3. In parallel, BMI increased from 27.1 to 31.1 kg/m² and body fat percentage from 36.7% to 41.1%. Inflammatory markers also rose across stages (hs-CRP: 3.9 to 6.1 mg/L; IL-6: 3.1 to 4.6 pg/mL). In multivariable models, higher DII scores were associated with increased pain severity (β=0.29, p=0.007) and higher hs-CRP levels (β=0.41, p<0.001), whereas Mediterranean diet adherence was positively associated with physical quality of life (β=0.34, p=0.002). Conclusion: Higher ultra-processed food consumption and dietary inflammatory potential were associated with increased inflammation, pain, and adiposity, whereas greater Mediterranean diet adherence was associated with better physical quality of life in women with lipedema.

BACKGROUND: Lipedema is a chronic and progressive adipose tissue disorder that is often misdiagnosed and notoriously resistant to weight loss. Liposuction remains the most effective surgical treatment, but it requires precise technique to preserve the fragile lymphatic system. This study investigates the utility of pre-, intra- and postoperative ultrasound (US) to objectively assess fat reduction and the selective removal of pathological adipose tissue in patients undergoing liposuction for lipedema. METHODS: A retrospective, single-center study of 24 female patients with lipedema who underwent liposuction of the lower extremities. Perioperative US was used to measure the thickness of the superficial subcutaneous fat (D1) and the deep fat layer (D2) at a standardized anatomical site. Intraoperative US was employed to verify that fat aspiration was performed in the correct superficial plane. A paired t-test was conducted to assess the statistical significance of the change in D1 thickness. RESULTS: The mean patient age was 38 years, with a mean BMI of 25.3 kg/m2. The mean volume of liposuction aspirate was 4.5 L. Statistical analysis showed a significant reduction in mean D1 thickness from 9.9 mm preoperatively to 6.3 mm immediately postoperatively (p < 0,05). This reduction was sustained at the 3-month follow-up, with a mean D1 thickness of 5.8 mm. CONCLUSION: Our pilot study suggests that the perioperative use of ultrasound is a valuable tool for objectively documenting the selective fat reduction achieved with liposuction in lipedema patients. Intraoperative US not only enhances surgical precision, but also reduces the risk of complications by confirming correct cannula positioning in the superficial plane. This technique enhances surgical precision by allowing for the quantifiable removal of pathological superficial fat, confirming its potential to improve outcomes with a low complication rate. LEVEL OF EVIDENCE IV: 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 .

Lipedema has long been misclassified as a cosmetic concern or a subtype of obesity, leading to delayed diagnosis and suboptimal surgical outcomes. Growing molecular, histopathologic, and imaging evidence supports lipedema as a systemic disorder involving adipose tissue, connective matrix, vascular–lymphatic integrity, and neuroimmune regulation. To integrate these findings into a clinically actionable model, we introduce the concept of Adipoconnective Fragility Syndrome (AFS), framing lipedema as a multisystem condition with direct implications for surgical planning and perioperative management.

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.

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.

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

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.

BACKGROUND: Lipedema is a chronic condition characterized by abnormal fat accumulation, primarily in the lower extremities, affecting mostly women. Despite improvements in diagnosis and treatment, lipedema is often misdiagnosed as obesity or lymphedema. Patients with obesity and lipedema propose a distinct clinical challenge in treating both diseases. Improved recognition and understanding are necessary to enhance diagnosis and treatment outcomes. PURPOSE OF THIS REVIEW: Lipedema is thought to be hormonally driven, often manifesting during puberty, pregnancy, or menopause. It presents as disproportionate fat accumulation in the lower body, often with microvascular changes. Misdiagnosis as obesity or lymphedema leads to ineffective treatments like weight loss programs and bariatric surgery. Effective management involves both conservative and surgical approaches, as well as a tailored strategy for patients with both lipedema and obesity. The focus of this review is to summarize the current literature addressing adequate treatment regimens for patients with both diseases and based on the literature we propose a treatment protocol. CONCLUSION: Patients with concurrent lipedema and obesity propose a distinct clinical challenge, in which early recognition can benefit adequate treatment. A combination of conservative measures and surgical options, particularly liposuction and/or bariatric and metabolic surgery, can be beneficial in treating patients with both diseases. However future research is needed to assess the effect of different treat regimens.

Lipedema is a chronic, progressive adipose tissue disorder characterized by disproportionate subcutaneous fat accumulation, pain, edema, and resistanc...

Background: Lymphedema is a debilitating condition with high morbidity, yet despite advances in management, diagnostic ambiguity and fragmented referr...

Lipoedema is a chronic disorder primarily affecting women. Often mistaken for obesity due to its characteristic build-up of fat cells in the legs and sometimes arms, lipoedema leaves women vulnerable to social stigma. This study investigated the role of fears of compassion and depressive symptoms in the context of weight stigma and internal weight bias in women with lipoedema.