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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, 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.

Review Article Background: Lipedema and advanced lymphedema are chronic disorders of adipose and lymphatic tissues that remain frequently underdiagnosed. Their coexistence poses therapeutic challenges, particularly when conservative management fails. Although international guidelines support surgical intervention in selected cases, real-world data from resourcelimited hospital settings remain scarce. Objective: To report the experience of a Moroccan tertiary university hospital in the surgical management of advanced lipedema and lymphedema and to compare clinical outcomes with current international recommendations. Methods: A retrospective descriptive case series was conducted between 2021 and 2024. Three patients underwent surgical treatment using tumescent liposuction or en bloc tissue resection with skin grafting. Postoperative outcomes were assessed clinically and through a structured quality-of-life questionnaire inspired by the SF-36, focusing on pain, mobility, and overall satisfaction. Results: All procedures were completed without intraoperative or postoperative complications. The volume of aspirated adipose tissue ranged from 2.1 to 4.0 L. One patient with advanced secondary lymphedema required surgical resection, with evacuation of 1.2 L of lymphorrhea. Postoperative satisfaction ranged from moderate to high, with reported quality-of-life scores between 5 and 8 out of 10. These findings are consistent with outcomes reported in recent international series. Conclusion: Surgical treatment of advanced lipedema and lymphedema is feasible, safe, and clinically beneficial, even in resource-limited settings. An individualized, guideline-based approach allows satisfactory functional and quality-of-life outcomes. Further prospective studies with standardized assessment tools are required.

Lipedema is a chronic adipose tissue disorder characterised by disproportionate accumulation of subcutaneous fat within specific anatomical depots, most commonly the lower extremities, with relative sparing of the trunk. Despite increasing clinical recognition, the mechanisms underlying the selective vulnerability of particular adipose depots and the progressive tissue remodelling observed in lipedema remain poorly understood. Emerging evidence suggests that lipedema is associated with complex alterations in adipocyte biology, adipose stem and progenitor cell (ASPC) function, immune signalling, vascular integrity, extracellular matrix remodelling, and lymphatic homeostasis, indicating that the disease extends beyond simple fat accumulation. Recent advances in adipose tissue biology have demonstrated that adipose depots are not functionally uniform structures, but rather anatomically distinct cellular ecosystems with unique developmental origins, transcriptional programs, stromal composition, immune niches, and metabolic properties. These depot-specific characteristics may provide an important framework for understanding the regional distribution and progression of lipedema. However, while substantial progress has been made in defining differences between visceral and subcutaneous adipose tissue, heterogeneity between individual subcutaneous depots remains comparatively underexplored despite its likely relevance to disorders of regional adipose expansion. The emergence of single-cell and spatial transcriptomic technologies has transformed the study of adipose tissue by enabling high-resolution mapping of adipocytes, stromal populations, vascular cells, and immune microenvironments within healthy and diseased tissue. These approaches offer an unprecedented opportunity to investigate depot-specific cellular states, intercellular signalling networks, and spatial tissue architecture in lipedema. In this review, we synthesise current evidence regarding tissue remodelling and adipose depot heterogeneity in lipedema and examine how single-cell and spatial omics approaches may advance mechanistic understanding of disease pathophysiology. We further discuss current technical and conceptual limitations within the field and highlight future directions for developing integrated adipose tissue atlases capable of identifying disease-driving cellular programs and therapeutic targets in lipedema.

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.

Lipedema is a chronic disorder characterized by abnormal subcutaneous fat accumulation, mainly in women's lower limbs. The aim of the study was to analyze the safety and efficacy of liposuction in treating lipedema. A systematic review was conducted in PubMed, Scopus, and MEDLINE until June 2024 using the terms "lipedema," "liposuction," "results," and "complications." Twenty-five studies were included (n = 2373 patients). Liposuction, mainly using the tumescent infiltration, reduced pain, BMI, and functional limitations, with improvements in mobility and quality of life. Mean aspirated fat volume was 3077 mL per session and 6111 mL per treatment course. Complications were uncommon (hematomas, edema, anemia, DVT, and rare methemoglobinemia). Moreover, improvements were maintained during the follow-up, suggesting that the beneficial results were sustained over time. Although 15 studies reported using tumescent, only 2 fully described the anesthetic fluid composition. Liposuction is a safe and effective treatment for lipedema, but variability in techniques and postoperative care highlights the need for standardized protocols and further research. Level of Evidence: 4 (Therapeutic).

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.

ObjectivesLipedema is a chronic condition that predominantly affects women, leading to painful, disproportionate fat distribution in the limbs. This systematic review and meta-analysis aimed to characterize health-related quality of life (HRQoL) across multiple domains in individuals with lipedema.MethodsWe systematically reviewed studies from inception to 3 July 2025 in MEDLINE (via PubMed) and Cochrane Controlled Register of Trials (CENTRAL) that primarily assessed HRQoL in individuals with lipedema. Data were extracted from studies using HRQoL assessment scales. The methodological quality of included studies was assessed using an adapted version of the Newcastle-Ottawa Scale for cross-sectional studies. The review protocol was pre-registered with PROSPERO (CRD42024590792). A random-effects meta-analysis was conducted to compute pooled mean HRQoL scores across various domains.ResultsFourteen cross-sectional studies involving nine countries and 3851 participants were included. The meta-analysis found significant impairments in multiple HRQoL domains: physical functioning (61.19, 95% CI: 56.77-65.60), pain (51.77, 95% CI: 45.01-58.53), social functioning (63.24, 95% CI: 58.44-68.04), emotional well-being (64.19, 95% CI: 59.86-68.52), and energy/fatigue (43.50, 95% CI: 39.32-47.68).ConclusionLipedema significantly affects HRQoL, with major deficits in physical, emotional, and social functioning. These findings highlight the need for greater clinical awareness and comprehensive management strategies, including both physical and psychological interventions, to improve the quality of life for individuals with lipedema. Further research is needed to explore long-term effects and optimize treatment approaches.

INTRODUCTION: Lipedema causes abnormal fat accumulation in the limbs, leading to pain, functional impairment, and body image disturbance. Nowadays, various liposuction techniques are available. The wet technique is increasingly being considered as the gold standard; however, comparative data between the dry and wet methods remain limited. We evaluated the efficacy of liposuction and compared outcomes between dry and wet approaches. Our analysis focused on surgical characteristics, complication rates, and clinical outcomes including pain relief, functional improvement, and esthetic satisfaction, with comparisons made between preoperative and 12-month postoperative results. METHODS: Besides surgical data extraction, patient-reported outcome measures (PROMs) were obtained through three different standardized questionnaires to assess pain relief, function gain, and esthetic satisfaction. RESULTS: Both techniques were effective, demonstrating overall improvements in pain, function, and body image, when comparing pre and postoperative outcomes. Lipoaspirate volumes were comparable between the groups. Operative time was significantly shorter in the wet technique group. Short-term complication rates did not differ between dry and wet techniques. While both techniques led to a global improvement, the wet technique showed greater potential in pain reduction and better esthetics satisfaction 12 months post-surgery. CONCLUSION: Lipedema is a complex disease that is still poorly understood. Liposuction may offer symptomatic relief regardless of the technique used, but the wet technique demonstrates better postoperative results, with improved PROMs and fewer complications. The treatment of lipedema requires a multidisciplinary approach, while conservative therapy remains the first-line option, surgical treatment by wet liposuction should be considered for its significant potential in improving functional outcomes and as an effective therapeutic option.

Background/Objectives: Lipedema is a chronic, progressive adipo-fascial disorder characterized by connective tissue dysfunction, fibrosis, microangiopathy, and adipose tissue proliferation. Although lipedema has traditionally been described as a regionally confined disorder, emerging evidence suggests that it may reflect a broader stromal and connective tissue dysfunction. It is therefore plausible that anatomical regions not historically associated with lipedema may also exhibit alterations consistent with this dysfunctional stromal pattern. From this perspective, breast tissue-rich in fibro-glandular and stromal components-represents a compelling model in which to investigate whether such features are present. The breast, with its complex fibro-glandular and stromal architecture, represents a physiologically plausible site of involvement; however, its structural features in lipedema have never been systematically examined. The primary aim of this study was therefore to determine whether breast tissue-rich in fibro-glandular and stromal components-shows recurrent imaging or histopathological features suggestive of lipedema-related involvement. A secondary aim was to compare the frequency of these findings with patterns typically reported in healthy screening populations. Methods: This retrospective cross-sectional study analyzed 62 women (mean age: 44 ± 8 years), obtained between September and November 2025, with a clinical diagnosis of lipedema who voluntarily provided breast imaging reports (ultrasound, mammography, or magnetic resonance imaging, MRI). Results: The findings revealed a remarkably high prevalence of fibro-glandular parenchyma (45%), multiple diffuse cysts (42%), microcalcifications (21%), and fibroadenomas (43.5%), with frequencies substantially exceeding those documented in healthy screening populations. Additional features included significant breast asymmetry or tuberous morphology (6%), reactive or sclero-lipomatous lymph nodes (19%), and recurrent stromal hyperplasia on biopsy. Histological evaluations (n = 9) consistently showed fibroproliferative alterations, including stromal hypercellularity, adenosis, fibroepithelial lesions, apocrine metaplasia, and pseudoangiomatous stromal hyperplasia, suggesting a shared extracellular matrix-related dysplastic phenotype between lipedema-affected breast tissue and peripheral adipose tissue. Conclusions: These findings support the hypothesis that lipedema may express a characteristic breast phenotype driven by stromal and extracellular matrix dysregulation. If confirmed in larger controlled studies, these recurrent alterations could contribute to improved diagnostic frameworks and raise awareness of lipedema as a systemic connective tissue disorder with underrecognized breast manifestations.

INTRODUCTION: Lipedema is a chronic inflammatory disease characterized by symmetrical deposition of adipose tissue in the upper and lower limbs, disproportionate to the trunk. It primarily affects women. The objective of this study was to evaluate the effects of surgical treatment in patients with lipedema who are refractory to conservative management. METHODS: We conducted a systematic review and single-arm meta-analysis in accordance with PRISMA guidelines. Retrospective studies involving patients who underwent surgical treatment after failing clinical management were included. Means and proportions were pooled using the inverse variance method and logit transformations, and heterogeneity was assessed using the I2 statistic. RESULTS: We included 6 studies comprising 429 patients, with follow-up ranging from 6 months to 44 months. In this meta-analysis, surgical treatment with tumescent liposuction resulted in significant clinical improvements for patients with lipedema. The pooled mean preoperative pain score was 5.64 (95% CI: 3.67-8.69), which decreased to 1.19 (95% CI: 0.91-4.22) postoperatively. Sensitivity to touch or pressure was reduced from a preoperative mean of 5.77 (95% CI: 4.10-8.10) to 1.96 (95% CI: 1.17-3.29) after surgery. Swelling scores improved from 5.47 (95% CI: 3.73-8.02) preoperatively to 2.14 (95% CI: 1.31-3.48) postoperatively, while restriction of movement scores decreased from 3.76 (95% CI: 2.48-5.72) to 0.77 (95% CI: 0.36-1.64). CONCLUSION: The results of this single-arm meta-analysis, which included six studies and 429 patients with lipedema refractory to clinical treatment and undergoing surgical intervention, demonstrate that tumescent liposuction is associated with reductions in postoperative pain and edema, as well as improvements in cosmetic outcomes, quality of life, and mobility. The duration of follow-up was adequate to capture relevant clinical outcomes and adverse events. However, lipedema remains a condition that requires further high-quality studies to define the optimal therapeutic approach. 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 ."

Background: Lipedema is a progressive disorder of subcutaneous connective tissue, predominantly affecting women, and characterized by an increase in subcutaneous adipose tissue, particularly in the lower body. This study aims to explore the gut microbiota (GM) profile in lipedema patients to characterize the associated GM and compare it with the control group. Methods: A prospective randomized case-control pilot study was conducted from September 2023 to May 2024, involving 55 Caucasian women, aged 20-60. The participants were divided into two groups: 35 with lipedema (LIPPY) and 20 controls (CTRL). Body composition was assessed using Dual X-ray Absorbimetry (DXA), and GM analysis was performed through 16S rRNA gene sequencing. Results: LIPPY subjects showed increased Intramuscular Adipose Tissue (IMAT) and reduced Lean Mass (LM)/Fat Mass (FM) ratios. While alpha and beta diversity metrics did not differ significantly between groups, differential abundance analysis identified a significant reduction in Eggerthellaceae (Log Fold Change (LFC) = -0.19, p = 0.04) and enrichment of Propionibacteriaceae (LFC = +0.18, p = 0.009) and Acidaminococcaceae (LFC = +0.32, p = 0.013) in the LIPPY group. Genus-level analysis showed a significant reduction in Blautia and Ruminiclostridium (LFC = -0.32 and -0.02; p = 0.02 and 0.04) and enrichment of Anaerostipes, Propionibacterium, and Phascolarctobacterium (LFC = +0.07, +0.17, and +0.34; p = 0.02, 0.005, 0.005, respectively). In correlation analyses, within LIPPY, Eggerthellaceae correlated negatively with Body Mass Index (BMI) (ρ = -0.61, p < 0.05) and positively with Appenicular (Appen) LM/Weight and AppenLM/BMI (ρ = +0.43 and +0.41, p < 0.05), while Anaerostipes correlated positively with these lean mass indices (ρ = +0.40, p < 0.05). In CTRL, only Anaerostipes showed a significant negative correlation with BMI (ρ = -0.64, p < 0.05). Conclusions: This study provides the first evidence of a distinct GM profile in LIPPY, with notable links to adverse body composition markers such as IMAT. Trial Registration: Trial registered on 24 June 2013 with ClinicalTrial.gov (NCT01890070).

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.