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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.

Lipedema in its various clinical stages is a condition that almost exclusively affects the female sex and appears at puberty. The oedema does not respond to common low-calorie diets, nor to exercise, nor to common anti-oedema medical therapies, nor to bariatric surgery. In the more advanced clinical stages, it can induce more or less important functional impairments that induce physical disability, as well as psychological, relational, and social discomfort: pain, functional walking impotence, easy muscular fatigability, sleep-wake rhythm disturbances also linked to the state of anxiety and depression that affects subjects in whom, often, the response to the treatments they are directed towards is practically nil. Many epidemiological, aetiopathogenetic, diagnostic, and clinical aspects still need to be studied in depth, considering, moreover, that the disease was only recognized with its own specific code by the World Health Organization in the 11th edition of the International Classification of Diseases on 1 January 2022.

Introduction  Lipedema is a chronic disease characterized by symmetrical and painful accumulation of subcutaneous fat, influenced by genetic and hormonal factors, and frequently misdiagnosed as obesity or lymphedema. Materials and Methods  In the present narrative review, we searched the PubMed and SciELO databases for articles published between 2015 and 2025, in Portuguese and English, addressing the diagnosis and the clinical or surgical management of lipedema. Results  In the PubMed search, we identified 299 studies, which were reduced to 106 after the removal of duplicates, with a progressive increase in publications since 2020; in the search on SciELO, we only retrieved 7 studies, all of which were also indexed in PubMed. The results reinforce that lipedema presents a complex pathophysiology, involving adipocyte hypertrophy and hyperplasia, chronic inflammation, microvascular dysfunction, and estrogen-related influence. International consensus indicates that diagnosis is essentially clinical, and that conservative treatment should be prioritized, including weight management, nutritional guidance, low-impact exercise, compression therapies, and psychosocial support. Surgical intervention, particularly tumescent or water-assisted liposuction techniques, is reserved for refractory cases and does not constitute a definitive cure. The growing alignment among consensus statements published over the past 5 years highlights the need for standardized diagnostic criteria and therapeutic protocols. Conclusion  The effective management of lipedema requires a multidisciplinary approach, continuous professional education, and strengthening of research that enable the establishment of evidence-based clinical guidelines. Keywordsdiagnosis; lipedema; literature review; surgery; treatment

Lipedema is a chronic and often debilitating adipose tissue disorder that primarily affects women. The disease is characterized by disproportionate and symmetrical accumulation of subcutaneous fat in the extremities. Despite the high prevalence of lipedema, which affects ∼10% of women, and its significant impact on patient quality of life, lipedema is understudied and often misdiagnosed as other disorders (obesity or lymphedema). In this review, we explore the current understanding of lipedema through clinical, tissue, and cellular lenses, and examine suspected pathological mechanisms, including hormonal influences (such as estrogen), adipocyte hypertrophy and hyperplasia, increased extracellular matrix (ECM) fibrosis, and specialized immune cell involvement, including M2 macrophage infiltration. Recent advancements in adipose tissue engineering, including organoids, fat-on-a-chip platforms, and the use of induced pluripotent stem cells (iPSCs) are explored as platforms to study lipedema pathogenesis.

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 lipoedema patients with obesity but does not consistently improve core lipoedema symptoms. Its role remains adjunctive rather than primary. Larger prospective studies using standardised definitions and outcome measures are needed to clarify its therapeutic value in this population.

Background/Objectives: Lipedema is a chronic disorder that affects almost exclusively women and is characterized by bilateral, symmetrical accumulation of subcutaneous fat, typically in the buttocks, hips, and lower limbs, and in some cases the arms. The primary objective of this study was to describe the clinical and anatomical manifestations of lipedema, together with the associated physical and psychological comorbidities, in a large Spanish cohort. Methods: Descriptive study of 1803 patients aged ≥ 17 years who attended two clinics in Spain between January 2022 and November 2024. Results: The mean age was 42.9 years (SD: 11.3), and 60.6% of patients were diagnosed during their reproductive years. The mean body mass index was 28.6 (SD: 6.2), and 87.6% presented a gynoid fat distribution. A total of 46.6% were classified as Schingale stage IV or V. The most frequent comorbidities were chronic low-grade inflammatory alterations and connective tissue damage. Particularly suspected high intestinal permeability (99%), bilateral trochanteric pain region (97.4%), iliotibial band involvement, and ligamentous hyperlaxity (95.8%). Thyroid disorders, inflammatory ovarian dysfunction, and psychological impairment were also common. Conclusions: Lipedema is a complex condition that extends beyond lower-limb adipose tissue and is associated with multiple comorbidities. This study also presents a novel approach to clinical assessment that may help physicians gain a deeper understanding of this pathology and formulate etiological hypotheses that will need to be tested.

Lipedema is a chronic adipose tissue disorder primarily affecting women, marked by abnormal, symmetrical, and disproportionate accumulation of subcutaneous fat in the lower limbs and sometimes in the arms, with hands and feet typically spared. Frequently misdiagnosed as lymphedema or obesity, lipedema presents with pain, easy bruising, bilateral nonpitting edema, and swelling that worsens throughout the day. We present two cases: Two middle-aged women reported longstanding bilateral lower limb swelling, pain, and varicose veins, without significant comorbidities. Clinical examination revealed characteristic disproportionate fat distribution and negative Stemmer's sign. Laboratory investigations and lymphoscintigraphy excluded other causes of edema. Imaging confirmed subcutaneous thickening, fat stranding, and varicosities. Both patients were advised to have conservative management including compression therapy, limb elevation, physiotherapy and dietary counseling; one exhibited significant limb volume reduction. Our report underscores the importance of recognizing lipedema for early diagnosis and effective management to prevent progression and complications.

Objectives: This study aimed to evaluate the clinical efficacy of transfer energy capacitive and resistive (TECAR) therapy in females with Stage 2 lipedema, focusing on limb circumference, pain, functional status, and quality of life. Patients and methods: A prospective, randomized controlled trial was conducted with 30 female patients diagnosed with Stage 2 lipedema between September 2024 and May 2025. Participants were randomized to a TECAR group (n=15; mean age: 52.7±13.1 years; range 39 to 66 years) or a control group (n=15; mean age: 45.9±12.9 years; range, 37 to 59 years). Both groups received compression garments and a structured exercise program. The TECAR group additionally underwent six TECAR sessions over three weeks. Outcomes included lower limb circumference, Visual Analog Scale for pain, Lower Extremity Functional Scale, and Lymphedema Quality of Life Questionnaire-Leg, assessed at baseline and at one and three months after treatment. Results: The groups were comparable at baseline for age (p=0.163) and body mass index (31.85±4.08 kg/m² in the TECAR group and 30.02±4.08 kg/m² in the control group; p=0.112). The TECAR therapy resulted in greater reductions in lower limb circumference compared to standard care, with a statistically significant and sustained improvement observed only in the supramalleolar region at three months (p<0.05). A significant short-term reduction in pain was observed at one month (p=0.003) only in the TECAR group, but this effect was not maintained at three months (p>0.05). Functional scores showed a nonsignificant trend toward improvement (p=0.058). The overall quality of life score improved significantly in the TECAR group (p=0.002), although no individual Lymphedema Quality of Life Questionnaire subdomain reached statistical significance (p>0.05). Conclusion: As an adjunct to standard care, TECAR therapy appears to reduce pain and limb volume and enhance overall quality of life in Stage 2 lipedema. Further long-term studies are needed to confirm these findings.

Background: Lipedema is a progressive adipofascial disorder marked by painful nodular fat deposition that is often mistaken for obesity. While tumescent liposuction reduces limb volume with relative lymphatic safety, persistent large, painful lobules frequently remain, and excisional strategies risk iatrogenic lymphatic injury. We evaluated the application of intraoperative indocyanine green (ICG) lymphography to identify and preserve lymphatic channels during debulking surgery for symptomatic lipedema. Methods: We conducted a single-center case series (University of Pittsburgh Medical Center, July 2023–December 2024) of adults with lipedema refractory to conservative therapy who underwent a selective dermato-lipectomy (lobule/skin excision) with or without tumescent liposuction. Patients with clinical lymphedema or dermal backflow in ICG were excluded. Near-infrared ICG (SPY-PHI) was used for pre-incision mapping and real-time intraoperative guidance; lymphatic trajectories were marked and spared during lobule excision. Primary measures included dermal backflow patterns and lymph node transit time; secondary outcomes were complications and symptom burden (Lymphedema Life Impact Scale, LLIS) through ≥24 months. Results: Eight patients (five female/three male; mean age 49.5 ± 14.4 years; median BMI 52.65 kg/m2) underwent ICG-guided surgery. Preoperatively, linear lymphatic patterns were visualized up to the knee in all patients, but dermal backflow patterns could not be visualized in 83% from the level of the knee to the groin. Still, 67% demonstrated inguinal nodal uptake (mean transit 24 min), suggesting preserved lymphatic transport. All cases achieved intraoperative confirmation of intact lymphatic flow after debulking. The mean liposuction aspirate was 925 ± 250 mL per lower extremity; the mean excision mass was 2209 ± 757 g per lower extremity. Complications included two superficial cellulitis events (25%) and one wound dehiscence (12.5%); no hematomas or skin necrosis occurred. No patient developed clinical or imaging evidence of iatrogenic lymphedema during follow-up. Conclusions: Intraoperative ICG lymphography is a practical adjunct for lymphatic-sparing debulking of symptomatic lipedema, enabling real-time identification and preservation of superficial collectors while addressing focal lobules. This hybrid approach—targeted tumescent liposuction followed by ICG-guided superficial dermato-lipectomy—was associated with meaningful symptom improvement and a low morbidity in this early series.

BACKGROUND: Lipedema is an abnormal accumulation of subcutaneous fat that usually affects the lower extremities. Inflammation due to adipose tissue may negatively affect body structure and functions. OBJECTIVE: This case-control study aimed to assess lower extremity muscle strength, endurance and function, functional exercise capacity, pressure pain threshold, and edema in women with lipedema and compare with healthy women. METHODS: Women with lipedema and healthy women of similar age and body mass index (BMI) were included in the study. Lower extremity muscle strength, muscle endurance, functionality, functional exercise capacity, pressure pain threshold, and edema (local tissue water) were assessed with digital dynamometer, 30-Second Sit to Stand Test (30-SSTS), Lower Extremity Functional Scale (LEFS), 6 Minute Walk Test (6MWT), manual algometer and skin moisture meter, respectively. RESULTS: Twenty-four women with lipedema (mean age: 47.9 ± 1.8 years, median BMI: 30.62 (19.03-41.20) kg/m2) and 20 healthy women (mean age: 47.2 ± 12.1 years, median BMI: 28.12 (23.23-39.66) kg/m2) participated in the study. Muscle strength for all assessing lower extremity muscles, 30-SSTS repetition number, LEFS score, pressure pain threshold of all assessing regions, percent of predicted 6MWT distance (p < .001) and 6MWT distance (p = .001) were significantly lower in women with lipedema compared to healthy controls. No significant difference was in terms of local tissue water percentage (p > .050). CONCLUSION: Lower extremity muscle strength, muscle endurance, functionality, functional exercise capacity and pressure pain threshold decrease in women with lipedema. It is recommended that these changes be taken into account when developing rehabilitation strategies.

Lipedema is a chronic adipose tissue disorder characterized by disproportionate fat accumulation, pain, and low-grade systemic inflammation, primarily affecting women. This study investigated the relationship between the Dietary Inflammatory Index (DII), adherence to the Mediterranean diet scores (MDS), inflammatory biomarkers (TNF-α and IL-6), and clinical outcomes in women with lipedema.

INTRODUCTION: Lipedema is a chronic female disease, characterized by an excessive accumulation of subcutaneous adipose tissue in the limbs and is commonly mistaken for obesity, although the two conditions often coexist. Obesity is associated with increased hedonic hunger and dysfunctional eating behavior. However, these aspects have not been investigated in females with lipedema and obesity. OBJECTIVES: The objective of this secondary analysis from a randomized controlled trial was to compare changes in hedonic hunger and eating behavior following two different low-energy diets, low-carbohydrate (CHO) or low-fat, in females with lipedema and obesity. METHODS: Females with lipedema and obesity (body mass index (BMI) 30-45 kg/m2) were randomized to two different low-energy diets (1,200 kcal), low-CHO diet (LCD) (75 g CHO) or low-fat diet (180 g CHO) for 8 weeks. Hedonic hunger was assessed using the power of food scale (PFS) and eating behavior was assessed using the Dutch Eating Behavior Questionnaire (DEBQ) pre- and post-intervention. RESULTS: A total of 70 females were included with a mean age of 47 years, and a BMI of 37 kg/m2. The LCD group reported a reduction in Food Present (p < 0.001) and in Aggregated Score (p = 0.035) from the PFS, while no changes were seen in the low-fat diet group, with changes in Food Present over time being significantly different between groups (p = 0.050). The low-fat diet group reported increases in Restrained Eating from the DEBQ (p = 0.036) while only the LCD group reported decreases in Diffuse Emotions (p = 0.040), however, no differences between groups were found. CONCLUSION: A LCD may induce more favorable changes in hedonic hunger and eating behavior than an isocaloric low-fat diet in females with lipedema, which may be related to altered metabolic signaling pathways related to satiety and reward.

Lipedema, a chronic condition primarily affecting women, is characterized by abnormal subcutaneous fat accumulation and swelling in the extremities (while sparing the hands, feet, and trunk). This disease is associated with genetic predisposition, hormonal imbalances, impaired lymphatic function, and vascular dysfunction. Lipedema does not directly cause weight gain, but excess weight can worsen symptoms and accelerate disease progression. Bariatric surgery is considered a treatment option for body weight management and reduction of subcutaneous fat; however, reported studies have indicated that this treatment cannot reduce localized fat accumulation or fat cell hypertrophy or alleviate pain symptoms. Although no proven dietary treatment currently exists, nutrition plays a key role in managing lipedema. Certain dietary approaches such as ketogenic, low-carbohydrate, and modified Mediterranean diets have been explored for weight management and inflammation reduction in lipedema, with studies showing positive effects on body composition and pain. However, according to the current literature no evidence-based nutritional treatments or nutritional supplements are effective in this patient group. Nutritional therapy in lipedema is complicated by frequent comorbidities; therefore, precision nutritional therapy should be planned by evaluating the causes and consequences of the disease. In this review, we evaluated reported studies of current evidence-based clinical nutritional approaches to lipedema treatment.

Liposuction is effective for body contouring but may cause transient cutaneous sensory changes. In lipedema, therapeutic liposuction involves higher aspirate volumes, fibrotic tissue, and exposure of distal-leg zones at risk. We hypothesized that postoperative sensory alterations are more frequent and persistent after lipedema surgery than after aesthetic lower-leg liposuction, with disease severity—rather than technique—driving outcomes.

Summary: Lipedema is a chronic disease characterized by the disproportionate and symptomatic accumulation of fat in the lower limbs and arms. Women with lipedema experience heaviness, fatigue and p...

I found the recent study by Alkhalfan et al. for identifying uric acid as a potential biomarker for lipedema and lymphedema through untargeted plasma metabolomics. To further enhance the clinical translation of these findings, I, propose a structured framework comprising baseline control characterization, longitudinal uric acid profiling across treatment phases, multi-analyte biomarker integration, and endocrine-based stratification. This approach aims to improve diagnostic specificity, accommodate inter-individual variability, and establish uric acid as a reliable tool in differentiating and monitoring lymphatic disorders.