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Aim: This narrative review summarises evidence on pathogenetic mechanisms of adipose tissue remodelling and adipokine dysregulation in lipedema, focusing on adipocyte hypertrophy and hyperplasia, fibrosis, microcirculatory and lymphatic dysfunction, immune-cell alterations, and diagnostic biomarkers. Methods: We conducted a narrative search in PubMed, Scopus, and Google Scholar from database inception to September 2026, including publications from 2001 to 2026. Search terms included “lipedema”, “lipedema adipokines”, “lipedema biomarkers”, “adipose tissue remodelling”, “fibrosis”, “adipocyte hypertrophy”, and “adipocyte hyperplasia”, combined with specific molecules. Bibliographies were screened. This review was not registered and did not follow a systematic-review protocol. Results: Lipedema involves pathological subcutaneous adipose tissue remodelling, including adipocyte hypertrophy and hyperplasia, extracellular matrix fibrosis, vascular alterations, and lymphatic dysfunction. Adipose tissue macrophages are enriched in CD163+/CD206+ populations, although the M1/M2 framework inadequately represents their heterogeneity. Individual adipokines (leptin, adipocyte-type fatty acid-binding protein) show limited diagnostic value due to dependence on total adipose mass and BMI. Multicomponent signatures (adiponectin, adipocyte-type fatty acid-binding protein, fibroblast growth factor 21, chemerin, afamin, growth and differentiation factor 15) demonstrate promising performance. Additional markers include reduced tissue adipsin expression, altered endostatin, and elevated interleukin-11, interleukin-28A, and interleukin-29. Most studies are limited by small cohorts, cross-sectional designs, inconsistent controls, obesity-related confounding, and lack of external validation. Conclusions: Lipedema involves coordinated metabolic, inflammatory, vascular, and extracellular-matrix alterations. Single adipokines are unreliable diagnostic biomarkers. Multicomponent panels may improve differentiation from obesity, but remain exploratory. Larger multicentre studies with standardised phenotyping and external validation are needed before clinical implementation.

Lipoedema is a painful adipose tissue disorder marked by disproportionate limb fat and often misclassified as generalized obesity or lymphoedema. This review examines its metabolic phenotype and implications for cardiometabolic assessment and management. PubMed/MEDLINE was searched from inception through May 2026 for studies on lipoedema, obesity, body composition, metabolic risk, insulin resistance, diabetes, lifestyle interventions, pharmacotherapy and liposuction. Relevant clinical, mechanistic, review and consensus literature was narratively synthesized. Evidence is limited and heterogeneous, consisting mainly of observational cohorts, referral‐centre series, mechanistic studies and consensus guidance, predominantly involving women. Some studies report fewer metabolic abnormalities in women with lipoedema than in women with BMI‐matched lifestyle‐related overweight or obesity. These findings do not establish metabolic protection and may reflect differences in central adiposity, disease stage, diagnostic criteria, body composition, inflammation or referral patterns. Obesity and glucose‐lowering therapies, including glucagon‐like peptide‐1 receptor agonists, remain appropriate for established indications, but direct modification of lipoedema has not been demonstrated. Cardiometabolic risk in lipoedema should be assessed using a phenotype‐based approach that distinguishes painful limb adiposity from central and ectopic fat while considering age, sex, menopausal status and established risk factors. BMI should be interpreted with waist measures, metabolic screening, body composition and muscle mass when relevant. Prospective studies using standardized diagnostic criteria, direct measures of insulin sensitivity, detailed body composition and clinically meaningful outcomes are needed to clarify long‐term risk and distinguish lipoedema biology from coexisting central obesity., Clinical recognition of the lipoedema phenotype and principal differential diagnoses.

Lipedema is a chronic disorder of subcutaneous adipose tissue characterized by symmetrical fat accumulation of the extremities and resistance to conventional weight loss. Therapeutic options remain limited, and clinical data on nutritional interventions are scarce. A 37-year-old woman with stage II lipedema underwent a ten-day medically supervised fasting program embedded in a multimodal intervention that also included physical activity after limited response to standard conservative management. Body weight decreased from 78.7 to 73.7kg, and C-reactive protein from 22.5 to 0.82mg/L. Limb circumferences decreased at the calves (48 to 44–44.5cm) and thighs (65 to 58cm). Subcutaneous tissue thickness, measured by ultrasound, decreased at the medial malleolus (22 to 12–15mm) and at the mid-thigh (44 to 34.5mm), while remaining stable in the gluteal region (98mm). Elastography showed a persistent heterogeneous fibrosclerotic pattern. The patient reported a marked reduction in pain (approximately 80% during fasting, sustained at ~50% for over one month). No adverse events occurred. Altogether, this case is notable because objective ultrasound measurements and inflammatory biomarkers improved after a structured fasting intervention in a condition usually considered resistant to weight loss. Because the intervention was multimodal, the contribution of fasting cannot be isolated and controlled studies are warranted. This suggests that medically supervised fasting may improve inflammatory status and tissue structure in lipedema and warrants further investigation in controlled studies.

The aim of this study was to compare serum adiponectin, leptin, resistin, irisin, and galectin-3 levels between patients with lipedema and healthy controls, and to examine their relationship with subcutaneous adipose tissue thickness.

Lipedema is a chronic adipose tissue disorder characterized by pain and disproportionate fat distribution. Although exercise is an important component of lipedema management, evidence regarding exercise behavior, physical activity, and related barriers remains limited. This study aimed to investigate exercise behavior, physical activity level, and perceived barriers in women with lipedema compared to healthy controls.

Background: The clinical course of lipedema in women receiving hormonal treatment for concomitant estrogen-dependent gynecological disorders remains insufficiently characterized. This study aimed to describe gynecological and lipedema-related manifestations during routine follow-up in women receiving subcutaneous gestrinone implants for gynecological indications. Methods: This retrospective, descriptive case series included 50 women with stage II or III lipedema and concomitant estrogen-dependent gynecological disorders treated between May 2024 and May 2025 at a specialized multidisciplinary outpatient clinic in São Paulo, Brazil. Participants received two biodegradable subcutaneous gestrinone implants (35 mg and 50 mg; total dose: 85 mg) exclusively for gynecological indications. Clinical outcomes were extracted retrospectively from medical records and analyzed descriptively. Improvement proportions were calculated using the number of patients presenting each manifestation at baseline as the denominator. Outcomes were based on patient reports and qualitative clinical assessments without standardized instruments. Results: Among gynecological manifestations, improvement was documented in 43 of 50 patients with menstrual pain (86%), six of 13 with menorrhagia (46.2%), and two of 50 with premenstrual symptoms (4%). Among lipedema-related manifestations, improvement was documented in 35 of 39 patients with edema (89.7%) and 33 of 41 with spontaneous pain (80.5%). Qualitative improvement in skin appearance and clinically assessed tissue fibrosis was documented in 31 of 50 (62%) and 28 of 50 (56%) patients, respectively. Overall clinical status was reported as improved by 42 patients (84%), stable by six (12%), and worsened by two (4%). Conclusions: Improvements in pain and edema, alongside qualitative changes in skin appearance and clinically assessed tissue fibrosis, were documented during routine follow-up. Given the retrospective design, absence of a comparison group, and nonstandardized assessments, these observations cannot be attributed to gestrinone or interpreted as evidence of its efficacy for lipedema. Prospective controlled studies using standardized outcome measures are warranted.

OBJECTIVE: To compare the efficacies of extracorporeal shock wave therapy (ESWT) and complex decongestive therapy (CDT) in patients with lipedema. DESIGN: This randomized-controlled-study included 33 patients with lipedema, with 11 patients in each of the three groups. The first group received ESWT alone, the second group received CDT alone, and the third group received ESWT followed by CDT within the session for six treatment sessions. Assessments were performed at baseline and two weeks after treatment completion. Outcome measures included total and lower extremity fat mass assessed using dual-energy X-ray absorptiometry, lower extremity volume, body mass index, pain intensity, pressure pain threshold, and quality of life. RESULTS: Total and lower extremity fat mass decreased significantly only in the ESWT and ESWT+CDT groups (P<0.05), although the magnitude of improvement was small and not superior to that of CDT alone (P>0.05). Additionally, all three groups showed significant improvements in lower extremity volume, pain intensity, pressure pain threshold, and quality of life (P<0.05), with no significant differences between the groups (P>0.05). CONCLUSION: All three treatment approaches are safe and feasible options for the management of lipedema. Considering its low cost, accessibility, and ease of application, ESWT may be preferred over the other treatment modalities.

BackgroundLipedema is a frequently misdiagnosed chronic condition that significantly impacts patients' quality of life. As artificial intelligence (AI)-based large language models (LLMs) become increasingly integrated into healthcare communication, their accuracy and consistency in providing patient-centered information require thorough evaluation, especially in rare diseases like lipedema. Therefore, this study aimed to evaluate the accuracy and reproducibility of responses generated by ChatGPT, DeepSeek, and Gemini to questions frequently asked by patients with lipedema.MethodsThis cross-sectional study assessed the accuracy and reproducibility of responses generated by ChatGPT, DeepSeek, and Gemini to 25 commonly asked lipedema-related questions. Each model was queried twice in separate sessions, and answers were evaluated by three independent experts using a four-point rating scale. To ensure the objectivity and consistency of expert evaluations, inter-rater agreement was assessed using Cohen's kappa coefficient.ResultsDeepSeek achieved the highest proportion of comprehensive and correct responses (72%), followed by Gemini (64%) and ChatGPT (56%). Accuracy varied across content categories, with notable limitations particularly in treatment, follow-up, and maintenance questions. Reproducibility analysis revealed that DeepSeek produced the most consistent responses across sessions, while ChatGPT and Gemini showed more variability, particularly in treatment and quality-of-life questions. Cohen's kappa values indicated high inter-rater agreement overall, with perfect agreement in some categories for ChatGPT and DeepSeek.ConclusionsLLMs can provide generally accurate and consistent responses to patient-centered questions about lipedema, particularly in areas related to general information and diagnosis. However, reduced accuracy and reproducibility in complex clinical domains suggest that expert oversight is essential when using these tools for patient education.

IntroductionAfter unification of diagnostic criteria for lipedema through guidelines and consensus documents as a fat-disproportion between abdomen and extremities with pain in the affected area, reduced by compression, expensive treatment options like liposuction should be reserved to affected women. Whilst the diagnosis of lipedema is obviously clinic, technical investigations or clear cut-offs shall help avoiding misuse of resources. The aim of this study was to find differentiation criteria between lipedema (LIP) controls (CO).MethodsInvestigator initiated exploratory investigation of 20 women per group, with interim analysis after completion of investigation of 10 women per group. 14 LIP and 12 CO were investigated with QOL-questionnaires (CIVIQ and Lymph), Wunstorf-Vein-Office anamnesis questionnaire, Visual Analogue Scale (VAS) of spontaneous pain, Pain under manual investigation, pain under compression cuffs, ultrasound of skin and subcutaneous fat tissue, share-wave-elastography, water content of skin (LymphScanner) and stiffness of skin (FibroScanner).ResultsStatistical evaluation between LIP and CO presented significant differences for all parameters excepting share-wave-elastography, water content and stiffness of the skin. Differences between controls and Lipedema were achieved with p < .0001 for the Wunstorf-Vein-Questionnaire, with p < .001 for CIVIQ (cut-off >40 Points for LIP), compression cuff (cut-off <60mmHG), with p < .01 Skin thickness (skin lateral thigh >2.1 mm in LIP), fat tissue thickness (ankle >18 mm).ConclusionThis first analysis could establish a series of clear cut-off values between lipedema and controls for medical history parameters (existence of pain and compliance with compression garments), pain sensitivity to palpation and pressure, and the results of at least one quality-of-life questionnaire (CIVIQ better than Lymph-QOL) and promising cut-offs for objective, technically measurable parameters, such as skin and subcutaneous fat thickness. The possibility to discriminate between lipedema and lipohypertrophy will be assessed in the second part of the investigation.

A previously healthy 35-year-old woman developed recurrent syncope and dyspnoea two days after extensive thigh liposuction for lipedema. CT pulmonary angiography revealed a large saddle embolus with peripheral emboli. Fat embolism was initially suspected; however, imaging findings and laboratory parameters supported a thromboembolic origin. Treatment with anticoagulation was complicated by postoperative bleeding. This case report highlights the importance of considering both fat embolism and thromboembolic pulmonary embolism after liposuction.

Lipedema is a chronic fibro-adipose disorder associated with pain, disproportionate limb enlargement, functional limitation, and impaired quality of life. Surgery has shifted toward technology-assisted approaches, but interpretation across platforms remains limited by inconsistent terminology, diagnostic criteria, outcome reporting, treatment-course definitions, and stage stratification. This review mapped reported outcomes across technology-assisted surgical platforms, emphasizing stage patterns, treatment burden, volume-related outcomes, complications, and lymphatic-related reporting.

To comprehensively characterize pain in women with lipedema and evaluate its relationship with central sensitization, neuropathic pain characteristics, pain sensitivity, sleep quality, and quality of life.: A cross-sectional controlled study.Department of Physical Medicine and Rehabilitation, Ankara Bilkent City Hospital.59 women with Type 2–3, Stage 1–3 lipedema and 59 age-matched healthy controls.Pain intensity, neuropathic pain characteristics, symptoms related to central sensitization, pain catastrophizing, sleep quality, health-related quality of life, and pressure pain thresholds were assessed using validated questionnaires and pressure algometry.Compared with healthy controls, women with lipedema had significantly higher pain intensity, painDETECT, Central Sensitization Inventory, pain catastrophizing, and sleep disturbance scores, whereas pressure pain thresholds and all Short Form-36 domain scores were significantly lower (all p &lt; 0.001). Clinically significant symptoms related to central sensitization (Central Sensitization Inventory ≥40) were present in 78.0% of patients versus 8.5% of controls. These associations remained significant after adjustment for age and body mass index. Although pain intensity, painDETECT scores, and pressure pain thresholds were associated with disease stage, Central Sensitization Inventory scores were not.Pain in lipedema extends beyond local adipose tissue changes and is associated with widespread pain sensitivity, symptoms related to central sensitization, impaired sleep, pain catastrophizing, and reduced quality of life. These findings support a multidimensional approach to pain assessment in lipedema.

BACKGROUND: Lipedema is a chronic adipose tissue disorder that may involve the upper extremities, particularly in advanced disease stages, leading to pain, heaviness, and functional complaints. While liposuction is an established treatment for symptom relief and volume reduction, its impact on objective upper-limb function-especially shoulder mobility-has not been systematically evaluated. METHODS: A prospective observational cohort study was conducted in female patients with upper-extremity lipedema undergoing circumferential arm liposuction. Active shoulder range of motion (ROM), including abduction, flexion, and external rotation, was assessed preoperatively and at 1, 3, 6, and 12 months postoperatively using standardized digital goniometry. Upper-limb disability (QuickDASH), pain, perceived heaviness, and upper-arm circumference were also recorded. Outcomes were analyzed over time and stratified by lipedema stage. RESULTS: Sixty-eight patients completed the 6-month primary follow-up. Mean active shoulder abduction improved significantly from 132.4° ± 13.8° at baseline to 154.7° ± 11.5° at 6 months and remained stable at 12 months (p < 0.001). Composite shoulder ROM demonstrated a similar progressive improvement. Patients with Stage II and III lipedema exhibited greater absolute functional gains, achieving postoperative ROM values comparable to those observed in earlier stages. QuickDASH scores, pain, and perceived heaviness decreased significantly over time (p < 0.001). Upper-arm circumference reduction correlated moderately with improvements in shoulder abduction (r = 0.42, p < 0.01). Measurement reliability was excellent (ICC ≥ 0.93). CONCLUSIONS: Upper-extremity liposuction for lipedema is associated with significant and durable improvements in shoulder mobility and upper-limb function. Beyond symptom relief and contour improvement, surgical debulking appears to restore functional movement, supporting the concept of upper-extremity lipedema as a functional disorder. Objective assessment of shoulder mobility should be considered an important outcome measure in the surgical evaluation of lipedema. 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 .

This cross-sectional and descriptive study was conducted with 395 women to assess lipedema awareness, lipedema symptom levels, and the screening probability of lipedema. Data were collected using an Introduction Form, and the Questionnaire and Screening Model for Lipedema. The mean score on the lipedema screening questionnaire was 6.05 ± 4.58. It was determined that 15.4% of women had a high probability of developing lipedema. We found that participants demonstrated awareness regarding lipedema and that sociodemographic characteristics were associated with lipedema risk.

Lipedema is a chronic, progressive, and often underdiagnosed disease characterized by the pathological, bilateral, and symmetrical accumulation of adipose tissue. This distribution results in disproportionate and painful swelling of the limbs. Typically extending distally from the hips, this predominantly female condition is frequently misidentified as lifestyle-induced obesity or bilateral lymphedema. This review aims to provide a comprehensive overview of the current understanding of structural and functional abnormalities in myocardial dimensions, mechanics, valves, and major arteries in patients with lipedema. According to the existing literature, left atrial enlargement, left ventricular rotational abnormalities, mitral annular dilation, and increased aortic stiffness have been identified in patients with lipedema. These findings suggest latent but significant alterations in left heart physiology. Although current data remain limited and are primarily focused on the left heart and the aorta, the rapid evolution of cardiac imaging technologies suggests that both clinical knowledge and the body of research in this field are poised for significant expansion.

Background Lipedema is a chronic medical condition primarily affecting women, characterized by bilateral, symmetrical, disproportionate fat deposition in the lower limbs, and sometimes arms and lower trunk. Pharmacological interventions remain limited, but glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dual GLP-1/glucose-dependent insulinotropic polypeptide receptor agonists (GLP-1/GIP RAs) could provide potential therapeutic benefit due to their effects on weight, metabolism, pain, and inflammation. Methods This was a cross-sectional, patient-reported online survey study comparing self-reported lipedema symptom severity, medication use history, and physical and mental health outcomes across three groups of women with lipedema stratified by GLP-1/GIP receptor agonist medication use status (current users, discontinued users, and never-users). The survey captured demographics, lipedema characteristics, medication use history, and intensity of lipedema symptoms. Additionally, the Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health-10 (PROMIS-10) instrument was used to assess physical and mental health. Analyses compared current users, discontinued users, and never-users of GLP-1/GIP RA medications. Results Of 2852 respondents, 2719 met inclusion criteria for analysis. Most participants (99.7%) identified as female, with a mean age of 52.4 years. Approximately 55% were current GLP-1/GIP RA users, most commonly taking tirzepatide. The primary reported reason for medication use was weight management (67.2%), followed by lipedema symptom management (19.3%). PROMIS-10 scores demonstrated higher physical and mental health ratings among current users compared with never-users (median Global Physical Health (GPH): 42.3 vs. 39.1; Global Mental Health (GMH): 44.9 vs. 40.8). Participants recalled improvements in both general health and lipedema symptoms after starting medication. Symptom severity scores for pain, swelling, and functional limitation were consistently lower among current users. Conclusions Self-reported participant responses indicated improved health and symptom severity while using GLP-1/GIP RA medication. These findings support further investigation of GLP-1/GIP RA medications as potential therapeutic options for lipedema.