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Lipoedema is a chronic adipose tissue disorder mainly affecting women with excess subcutaneous fat deposition on the lower limbs, associated with pain and tenderness. There is often a family history of lipoedema, suggesting a genetic origin, but the contribution of genetics is not well studied. We conducted a genome-wide association study (GWAS) for this disorder in a clinically ascertained cohort from Spain and performed a meta-analysis with the UK lipoedema cohort GWAS. We then used the results of this study as a replication of the inferred UK Biobank “lipoedema phenotype” study. Whilst our meta-analysis alone did not identify any genome-wide significant associations, our clinical cohorts provide support for three loci identified through the UKBB study: the chr2q24.3 GRB14-COBLL1 locus (rs6753142, PMETA=1.64x10-6), chr6p21.1 VEGFA locus (rs4711750, PMETA=8.99x10-7) and the chr5q11.2 ANKRD55-MAP3K1 locus (rs3936510, PMETA=1.67x10-5). We identify numerous rare SNPs with strong association signals in our meta-analysis (P<1x10-6) with support in both UK and Spanish datasets, three of which also show nominal support in the UKBB (P<0.05). These findings provide a starting point towards understanding the genetic basis of clinical lipoedema and demonstrate the utility of the interplay of large-scale biobanks genetic data and clinically ascertained cohorts to elucidate the genetic architecture of lipoedema.

Background: Lipedema is a chronic adipose tissue disorder predominantly affecting women and is frequently misclassified as obesity. While its physical manifestations are increasingly recognized, less attention has been paid to eating attitudes and psychological well-being in this population. The objective of this study was to descriptively explore eating attitudes and psychological well-being in women with lipedema.Methods:This exploratory cross-sectional study used an anonymous online survey to describe eating attitudes and psychological well-being in women with lipedema. A total of 47 participants completed the Eating Attitudes Test (EAT-26) and the World Health Organization-5 Well-Being Index (WHO-5). Descriptive statistics were used to summarize screening indicators of disordered eating risk and reduced psychological well-being.Results:Approximately two-thirds of participants scored at or above the EAT-26 screening cut-off, reflecting elevated screening indicators of disordered eating risk. When behavioral risk indicators were included, over 70% screened positive according to EAT-26 criteria. Reduced psychological well-being (as indicated by a WHO-5 score of ≤50) was observed in about one-fifth of the sample.Conclusion:In this exploratory sample of women with lipedema, elevated screening indicators of disordered eating risk and reduced psychological well-being were commonly observed. These findings offer preliminary insights suggesting that eating-related risk and reduced well-being may be prevalent in this population. Further research using larger, clinically verified samples is needed to better understand the psychological aspects of lipedema.

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.

Background Lipedema is characterized by disproportionate gluteofemoral adiposity with anti-inflammatory properties. We hypothesized that this phenotype may confer immunological protection against T-helper 1 (Th1)-mediated autoimmunity ("Immunological Shield Hypothesis"). Objective The objective of this study is to explore whether women with a dual-energy X-ray absorptiometry (DXA)-defined lipedema-like phenotype, characterized by disproportionate gluteofemoral fat accumulation, exhibit distinct immunometabolic profiles and lower prevalence of celiac disease (CD) autoimmunity in a nationally representative sample. Methods The cross-sectional analysis included 3,833 women from the National Health and Nutrition Examination Survey (NHANES) 2011-2014. Celiac disease (n=11, 0.56% weighted prevalence) was defined by strict serology (tissue transglutaminase {tTG}-IgA+/endomysial antibody {EMA}-IgA+); lipedema phenotype was defined as leg-to-trunk fat ratio of >90th percentile via DXA. Results Women with celiac disease exhibited 7.4% lower gynoid fat (39.5% versus 42.6%, p=0.0007), persisting in overweight/obese strata. Conversely, the lipedema phenotype demonstrated superior metabolic health: 44.2% lower homeostatic model assessment of insulin resistance (HOMA-IR) (p<0.001) and 7.6% lower neutrophil-to-lymphocyte ratio (NLR) (p=0.012). Conclusions This exploratory population-based analysis identifies phenotypic divergence in fat distribution between the DXA-defined lipedema phenotype and celiac disease autoimmunity, yielding observations consistent with, but not confirmatory of, the "Immunological Shield Hypothesis." While limited by the small number of celiac cases (n=11), a sample size insufficient to detect prevalence differences for a ~7%-9% phenotype, for which approximately 225-600 celiac cases would be required, the observed differences in gynoid adiposity (7.4% reduction, p=0.0007) and the favorable metabolic profile of the lipedema phenotype (44.2% lower HOMA-IR and 7.6% lower NLR) suggest biological plausibility warranting validation in larger, targeted cohorts. These findings motivate targeted studies to evaluate whether dietary exposures, including gluten-related immune activation, interact with gluteofemoral adipose biology in lipedema.

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Lipoedema is a chronic, progressive condition characterised by disproportionate fat accumulation in the lower extremities, often misdiagnosed due to symptom overlap with obesity. Weight management is a key component of lipoedema treatment, yet the role of bariatric surgery remains unclear. This systematic review evaluates the impact of bariatric and metabolic surgery (BMS) on lipoedema symptoms, weight loss outcomes, and the need for further interventions. A systematic search of PubMed, Scopus and the Cochrane Library was conducted up to January 2025 following PRISMA guidelines. Studies reporting on patients with lipoedema (or equivalent diagnoses) who underwent BMS were included. Quality was assessed using the Joanna Briggs Institute (JBI) checklist for case reports and the National Heart, Lung and Blood Institute (NHLBI) tool for case series. Seven studies met the inclusion criteria (five case reports, two cohort studies), comprising 51 patients. All underwent BMS, primarily sleeve gastrectomy or Roux-en-Y gastric bypass. One study (n = 31) reported a significant reduction in thigh volume and weight loss comparable to controls. The remaining studies found persistent or worsened lower body disproportionality and no improvement in pain. Postoperative lipoedema diagnoses were common, raising concerns over diagnostic accuracy. Overall weight loss averaged 33.9% total weight loss. Bariatric and metabolic surgery achieves meaningful weight reduction in patients with lipoedema and obesity but does not consistently improve core lipoedema symptoms. Its role remains adjunctive rather than primary. Preoperative identification and documentation of lipoedema features are recommended, with a postoperative plan for adjunct conservative therapies and selective consideration of lymph-sparing liposuction where symptoms persist. Larger prospective studies using standardised definitions and outcome measures are needed to clarify its therapeutic value in this population.

Lipedema is a multifactorial disorder with a negative evolutionary trend, influenced by genetic, hormonal, metabolic, and vascular factors that are not fully understood. Inflammation is a typical feature of lipedema and can be managed by limiting glycemic spikes. Herein, we report the case of a patient diagnosed with lipedema who followed a ketogenic diet (KD) for 6 months, resulting in a weight loss of 12 kg. Afterward, she transitioned to a low-carbohydrate (LC) diet for an additional 6 months, maintaining the good results achieved in terms of quality of life (QoL) improvement, weight control, and pain management. The patient regularly engaged in resistance training, which preserved and improved muscle mass. The primary and new outcome was due to the introduction of the second phase of the nutritional plan, specifically the low-carbohydrate diet, which could be an innovative approach. Often, diets that contain standard amounts of carbohydrates do not yield appreciable results.

Lipedema is a chronic and progressive disorder characterized by disproportionate fat accumulation, mainly affecting the lower extremities of women, and commonly accompanied by sensations of heaviness, tenderness, and discomfort. While its pathogenesis remains largely unknown, genetic, hormonal, and microvascular factors have been implicated. The condition often coexists with psychological distress, which significantly detracts from the quality of life of affected individuals. Diagnosis is primarily clinical, as no specific biomarkers or imaging modalities have been proven sufficiently reliable for identification. Proposed managements are controversial, although current treatment focuses on symptom management and disease control through conservative methods such as compression and non-invasive device therapies, specialized diets, and physical rehabilitation or surgical treatments. Psychological support is vital in addressing the emotional challenges of the condition. Despite recent advancements in the understanding and management of lipedema, there remains a critical need for further research to establish standardized diagnostic criteria and targeted therapeutic strategies for this debilitating condition.

Background: Emerging evidence suggests that lipedema may share hormonal, inflammatory, and genetic mechanisms with gynecologic diseases, particularly endometriosis. However, the extent and nature of these interrelationships remain poorly characterized, supporting the need for this scoping review. Objectives: To map and synthesize the available evidence on the clinical, pathophysiological, and epidemiological interrelationships between lipedema in women, endometriosis, and other gynecologic diseases. Methods: Searches were conducted in international and regional health databases, including MEDLINE (PubMed), CINAHL, Scopus, Embase, Web of Science, the Cochrane Library, LILACS/VHL, APA PsycInfo, SciELO, Epistemonikos, and La Referencia, as well as grey literature sources and relevant institutional websites. There were no language restrictions. The search period began in 1940, the year in which lipedema was first described by Allen and Hines. Study selection followed a two-stage process conducted independently by two reviewers, consisting of title and abstract screening followed by full-text review. Data extraction was performed using a pre-developed and peer-reviewed instrument covering participants, concept, context, study methods, and main findings. The review protocol was registered in the Open Science Framework. Results: Twenty-five studies from ten countries were included. Synthesized evidence supports the characterization of lipedema as a systemic condition with metabolic and hormonal dimensions. Key findings include symptom onset linked to reproductive milestones, a high frequency of gynecologic and endocrine comorbidities, and molecular features overlapping with steroid-dependent pathologies. These patterns reflect a recent shift from a predominantly lymphovascular paradigm toward a more integrated endocrinometabolic framework. Conclusions: The findings indicate that lipedema clusters with hormone-sensitive gynecologic and endocrine features across reproductive life stages.

Background. Lipedema is a chronic and progressive fat disorder that affects ~11% of the female population. It is characterized by bilateral, disproportionate accumulation of subcutaneous adipose tissue predominantly in the lower body. Symptoms include pain, bruising, swelling, and subcutaneous nodules that are resistant to traditional interventions such as diet and exercise. Aim. The objective of this review is to summarize recent evidence on the characteristics, pathophysiology, diagnosis and treatment of lipedema. Matherial and Methods. A literature search was conducted using the PubMed database. The inclusion criteria were “full free text” and English scientific articles, published between 2015 and 2025. A total of 74 records were found, of which&nbsp; &nbsp; publications were ultimately included in the review. Results. Awareness of lipedema in the medical field is increasing, but its differential diagnosis still remains a challenge. Lipedema is often unrecognized or misdiagnosed as obesity or lymphedema. Conclusion. This narrative review provides a deeper understanding of lipedema as a serious condition, discusses its pathophysiology and treatment options. The data reveal advances in knowledge, particularly in conservative and surgical treatment with a focus on improving quality of life. However, there is a lack of scientific evidence confirming the safety and efficacy of various treatment methods. Further research is required to ensure the safety and increase the efficacy of treatment for this complex condition known as lipedema.

Background:  Lipedema is a progressive subcutaneous adipose tissue disorder predominantly affecting women. Characterized by painful nodules and inflammation, it impairs mobility and quality of life. Traditional nonsurgical treatments currently offer limited relief and necessitate additional interventions. This study aimed to evaluate the efficacy of SMiLE (Softening, Mobilization, Liposuction, Extraction), a lipedema reduction surgery (LRS) technique. This technique combines lymphatic-sparing liposuction with manual lipedema extraction to comprehensively remove lipedema nodules. Methods:  Sixty-two women who underwent LRS with the SMiLE technique by the primary author participated in the study and completed an online survey. Data were collected on prior medical history related to lipedema development and comorbidities and outcome measures such as pain, activities of daily living, and quality of life before and after surgery. Results:  The findings demonstrate significant improvements in patients’ daily lives following surgery. Pain levels decreased by an average of 73.9%, with the most notable reduction in the buttock shelf (81.3%). Mobility improved for 93% of participants who had faced challenges before LRS, and quality-of-life assessments indicated a 47.5% reduction in the negative impact of lipedema postsurgery. Conclusions:  The SMiLE technique offers an advancement in the surgical management of lipedema by enabling the effective removal of lipedema tissue. Alongside a reduction in pain and improvement in mobility, this method addresses physical and psychological burdens. This study suggested that the SMiLE technique could be considered an option as part of a comprehensive approach to treating patients with lipedema.

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Objective: The aim of this study was to identify the demographic and clinical characteristics of patients with lipedema who presented to our outpatient clinic in Çorum, thereby contributing to defining the lipedema case profile in our country. Material and Methods: We included 80 female patients diagnosed with lipedema at the physical medicine and rehabilitation outpatient clinic of our hospital between January 2020-July 2023. Data on age, body mass index (BMI), lipedema type-stage, and symptoms were collected from medical records. Laboratory evaluations, including hemogram, 25-OH vitamin D, vitamin B12, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and lower limb venous doppler ultrasound results were also obtained from medical records. Results: The mean age was 46.46±9.72 years and BMI was 32.12±4.84. Type 2 lipedema was the most common, followed by Type 1 and Type 3. Stage 2 lipedema was seen in 63.8% of the patients, stage 1 in 21.2%, and stage 3 in 15%. Common symptoms included pain, swelling, fatigue, and leg heaviness. The mean CRP was 4.88±2.89 mg/L, ESR was 18.58±10.06 mm/h, 25-OH vitamin D was 18.73±12.95 ng/dl, and vitamin B12 was 359.74±155.12 pg/ml. Venous insufficiency was present in 50% of the patients. Lipedema stage showed significant positive correlations with age (r: 0.284, p: 0.011), BMI (r: 0.307, p: 0.006), and ESR (r: 0.271, p: 0.015).Conclusion: Patients presenting with swelling and pain in the lower limbs should always be assessed for lipedema, and it should also be considered that venous insufficiency and vitamin deficiencies may coexist in these patients.

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BACKGROUND: Lipedema is a chronic adipose tissue disorder with disproportionate fat accumulation in the extremities and is often misdiagnosed as obesity. Although women with lipedema appear to be metabolically distinct from body mass index (BMI)-matched controls, their fasting metabolism remains insufficiently characterized. We therefore aimed to define the metabolic signature of lipedema using serum NMR metabolomics and anthropometric profiling. METHODS: We conducted a study with 24 premenopausal women with lipedema and 21 BMI-matched controls. Fasting serum samples were analyzed using NMR spectroscopy and anthropometric data were collected. Regional body composition was additionally assessed in an exploratory matched DXA subset (n=12). To characterize coordinated metabolic differences beyond single analytes, we derived exploratory composite indices and applied multivariate analyses. RESULTS: Despite similar BMI, women with lipedema showed lower waist circumference, waist-to-hip ratio and lower fasting insulin than controls (age-adjusted p = 0.032). NMR profiling revealed lower alanine (p < 0.001), lactate (p = 0.004), pyruvate (p = 0.021), and elevated ketone bodies (3-hydroxybutyric acid: p = 0.009; acetoacetic acid: p = 0.035; acetone: p = 0.006). These alterations were reflected by significant group differences in composite indices for fat distribution (g = 1.26; p < 0.001), glycolysis (g = 0.74; p = 0.018), and ketone metabolism (g = 0.70; p = 0.018). Principal component analysis of the selected indices explained 78% of the total variance and showed partial group separation between lipedema and controls. CONCLUSION: Lipedema is associated with a distinct fasting metabolic profile characterized by reduced glycolytic intermediates, enhanced ketone body signals, and a more peripheral fat distribution despite comparable BMI. These findings support the concept of lipedema as a metabolically distinct phenotype and suggest that multivariate metabolic signatures may help refine future diagnostic and interventional approaches.

Lipedema is a chronic inflammatory disorder of adipose tissue that predominantly affects women and is characterized by disproportionate subcutaneous fat accumulation, pain, spontaneous bruising, and significantly impaired quality of life. Although hormonal influences on its pathophysiology have been increasingly recognized, evidence-based treatment options remain limited. Recently, gestrinone has been proposed as an off-label therapy based on hormonal mechanistic hypotheses. A critical narrative review of the literature was conducted using international databases to identify clinical or pharmacological evidence supporting its use in lipedema. No clinical trials, observational studies, case series, or case reports directly evaluating this therapy were identified. Existing proposals rely exclusively on theoretical extrapolations lacking clinical validation. Therefore, current evidence does not support the use of gestrinone in the treatment of lipedema, and its use should be considered experimental until adequately designed clinical studies are available.Keywords: lipedema; adipose tissue; hormone therapy; gestrinone; evidence-based medicine

Lipedema is a chronic, female-predominant disorder of subcutaneous adipose tissue characterized by disproportionate fat expansion, pain, and fibrosis. Despite its high prevalence, the cellular mechanisms underlying lipedema remain poorly understood. While the clinical features have been extensively described, its biology of adipose tissue dysfunction and aberrant intercellular communication is still unclear. In comparison to obesity, lipedema is marked by local dysregulation of adipocyte-stromal and adipocyte-vascular interactions. In this hypothesis perspective, we discuss emerging mechanistic concepts from a cell biology perspective that are particularly relevant to lipedema, focusing on (i) organelle contact site dynamics in adipocytes and their role in lipid handling and stress adaptation; (ii) extracellular vesicle (EV)-mediated crosstalk between endothelial cells, adipocytes, and immune cells as a driver of localized inflammation and fibrosis; and (iii) estrogen-linked signaling pathways that may imprint EV cargo and cellular behavior in a sex-specific manner. By integrating these perspectives, we highlight open experimental settings and mechanistic parallels to other adipose tissue pathologies that help understanding lipedema as a distinct cellular and molecular entity. Investigating how organelle biology, extracellular vesicles communication and hormonal context intersect in adipose tissue may uncover novel biomarkers and therapeutic entry points for this long-neglected condition.