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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.

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 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 ."

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.

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...

Lipedema is a chronic disorder characterized by the symmetrical accumulation of subcutaneous adipose tissue, predominantly affecting women. Despite increasing recognition, the pathophysiological mechanisms underlying adipose tissue dysfunction in lipedema remain incompletely understood. This mini review combines current knowledge about adipose tissue biology in lipedema, highlighting recent discoveries, ongoing controversies, and future research directions. A comprehensive literature review was conducted focusing on adipose tissue-related research in lipedema with emphasis on pathophysiological mechanisms, cellular composition, and therapeutic implications. Recent studies reveal that lipedema adipose tissue exhibits distinct characteristics, including M2 macrophage predominance, stage-dependent adipocyte hypertrophy, progressive fibrosis, and altered lymphatic/vascular function. The inflammatory profile differs markedly from obesity, with an anti-inflammatory M2-like macrophage phenotype rather than the pro-inflammatory M1 response seen in classic obesity. Emerging evidence suggests lipedema may represent a model of “healthy” subcutaneous adipose tissue expansion with preserved metabolic function despite increased adiposity. Current research proposes menopause as a critical turning point, driven by estrogen receptor imbalance and intracrine estrogen excess. Lipedema represents a unique adipose tissue disorder distinct from obesity, characterized by specific cellular and molecular signatures. Current research gaps include the need for validated biomarkers, standardized diagnostic criteria, and targeted therapeutics. Future research should focus on elucidating the molecular mechanisms driving adipose tissue dysfunction and developing precision medicine approaches.

Lipedema is a chronic, progressive adipose tissue disorder that affects up to 10% of women and is characterized by disproportionate lower-limb fat accumulation, pain, edema, and resistance to conventional weight-loss approaches. Its pathophysiology involves a complex interplay of adipocyte hypertrophy, chronic inflammation, extracellular matrix fibrosis, mitochondrial dysfunction, and sex steroid imbalance, highlighting the need for disease-modifying therapies. This narrative review synthesizes mechanistic, translational, and clinical evidence linking metabolic, inflammatory, and fibrotic pathways to lipedema and tirzepatide's potential therapeutic relevance. Tirzepatide, a dual GLP-1 (Glucagon-Like Peptide-1)/GIP (Glucose-Dependent Insulinotropic Polypeptide) receptor agonist, has demonstrated unprecedented efficacy in obesity and diabetes, alongside pleiotropic actions on inflammation, fibrosis, and adipose remodeling. Mechanistic studies reveal favorable effects on macrophage polarization, cytokine signaling, extracellular matrix turnover, and thermogenesis, suggesting potential relevance to lipedema biology. Translational evidence from related fibro-inflammatory conditions such as steatohepatitis and heart failure further supports its antifibrotic and immunomodulatory plausibility. Although direct clinical evidence in lipedema is lacking, the convergence of mechanistic pathways provides a strong rationale to investigate tirzepatide as a disease-modifying candidate. If future clinical studies confirm these mechanisms, tirzepatide could represent a novel metabolic-hormonal therapy capable of modifying the natural course of lipedema.

Lipedema is a chronic, progressive disorder marked by the abnormal accumulation of subcutaneous adipose tissue, predominantly in the lower body and almost exclusively affecting women. In recent years, the off-label use of gestrinone - a synthetic steroid with androgenic, antiprogestogenic, and weak estrogenic activity, originally approved only for endometriosis - has gained attention as a potential therapy for lipedema, particularly in the form of subcutaneous implants. This systematic review aimed to assess the efficacy and safety of gestrinone for this indication. A systematic literature search was conducted in PubMed, MEDLINE, Cochrane Library, and LILACS; clinical trial registries (ClinicalTrials.gov and Brazilian Registry of Clinical Trials (ReBEC)); as well as national and international clinical guidelines and expert consensus documents published up to July 30, 2025, following PRISMA guidelines. Eligible studies included randomized trials, observational studies, systematic reviews, case series, and clinical guidelines. Study selection, data extraction, and quality assessment were performed independently by two reviewers, with a third resolving discrepancies. The search identified nine records across all databases, registries, and other sources. After removing one duplicate, eight unique records were screened. All four records from indexed databases underwent full-text assessment. After applying inclusion/exclusion criteria, no studies - randomized, observational, or otherwise - were identified that evaluated the use of gestrinone for lipedema. Likewise, no ongoing clinical trials were found. Clinical guidelines and position statements from professional societies and patient associations uniformly advise against the off-label prescription of gestrinone for lipedema, citing the absence of scientific evidence. There is no scientific basis for the use of gestrinone in the management of lipedema. Healthcare providers should rely on evidence-based treatments, including compression therapy, tailored physical exercise, nutritional counseling, and psychological support and restrict hormonal interventions to ethically approved research protocols.

Knee pain in women with lipedema is frequently misattributed and undertreated. We outline a biomechanical and inflammatory cascade linking systemic adipose dysfunction, anabolic resistance, and thigh-predominant sarcopenia to dynamic knee valgus, plantar arch collapse, altered gait, patellofemoral malalignment, and ultimately chondromalacia patellae. We integrate synovial-adipose crosstalk and the high prevalence of generalized joint hypermobility as amplifiers of joint loading. This framework supports a practical, staged approach that couples symptom control with progressive, targeted strengthening and gait retraining. Rather than treating the knee in isolation, addressing the cascade may reduce pain and improve function.

This article aims to summarize contemporary understanding and management strategies of lipedema. It will elucidate recent advancements in diagnostic methodologies, the role of imaging technologies, and evolving therapeutic interventions. The article will further delineate critical areas that warrant further investigation.

Introduction: Lipedema is a chronic, progressive loose–connective-tissue disorder characterized by painful, disproportionate subcutaneous adipose tissue, functional limitations, and impaired quality of life, prompting growing interest in evidence-based management strategies. Objective: To systematically review contemporary human studies on surgical and non-surgical treatments for lipedema, with emphasis on symptom control, functional outcomes, complications, and quality of life, and to synthesize comparative effectiveness across modalities. Methods: We planned a PRISMA-compliant search of PubMed, Scopus, Web of Science, Cochrane Library, LILACS, ClinicalTrials.gov, and ICTRP for the last five years, expanding to ten years only if fewer than ten eligible studies were found; inclusion criteria prioritized human clinical trials and observational studies, with basic science excluded from synthesis; risk of bias and certainty of evidence (GRADE) were prespecified; data were extracted for populations, interventions, comparators, outcomes, and follow-up. Results and Discussion: Recent literature suggests that compression therapy, exercise, and pneumatic compression can reduce pain and edema and improve patient-reported outcomes, while liposuction techniques including tumescent, power-assisted, and water-assisted approaches generally show substantial improvements in symptoms and health-related quality of life with acceptable complication rates; however, heterogeneity in diagnostic criteria, outcome measures, and follow-up limits certainty of pooled estimates. Conclusion: Contemporary evidence supports a stepped, individualized approach beginning with optimized conservative care and progressing to lipedema reduction surgery in appropriately selected patients, with shared decision-making and standardized outcome measurement essential for practice and future research.  

Lipoedema is a chronic condition that manifests in the body as excessive fat buildup, primarily deposited in the legs, hips, buttocks, and sometimes in the

Background Lipedema is a chronic, progressive condition characterized by symmetrical accumulation of adipose tissue, predominantly in women's lower extremities. It is frequently associated with pain, reduced mobility, and psychological distress. Dietary interventions have become central to conservative management of the condition, yet their clinical efficacy remains unclear. Methods This systematic review included peer-reviewed studies assessing dietary strategies in individuals with clinically diagnosed lipedema. Searches were conducted in four databases in July 2025, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Eligible studies applied dietary interventions and reported clinical or psychosocial outcomes, and the risk of bias was subsequently assessed. Results Nine studies involving 269 women met the inclusion criteria. The majority applied hypocaloric dietary protocols, particularly ketogenic, low-carbohydrate high-fat, or ketogenic modified Mediterranean diets. Across studies, weight loss and reduction in fat mass were consistently reported. Some studies also observed improvements in pain, inflammation, and quality of life, though these outcomes were not uniformly assessed. Few studies used advanced measures of body composition such as dual-energy X-ray absorptiometry or magnetic resonance imaging; most relied on bioelectrical impedance analysis. Only one study evaluated emotional dysregulation and only one assessed food addiction, but no study systematically measured eating behavior traits, or current or past eating disorders. Intervention durations ranged from four to twenty-eight weeks, and adherence strategies varied. The risk of bias was moderate to high in most studies. Two trials (conducted by Lundanes and Jeziorek et al.) were randomized controlled trials, whereas the remaining studies used non-randomized designs despite including control and intervention groups. Due to the high heterogeneity in study design, outcomes, and measurement tools, combined with the small sample sizes and risk of bias, it was not possible to conduct a meta-analysis. Conclusion The effects of dietary approaches on lipedema remain unclear. Future studies should adopt robust methodological designs, include larger and stratified samples based on disease stage, use accurate assessments of body composition (including muscle mass and strength), evaluate mental health and eating behaviors, and investigate the long-term sustainability of interventions. The literature lacks standardized methodologies and comprehensive evaluation of psychosocial and eating behavior, highlighting the need for stronger evidence to inform clinical practice.

Lipedema is a chronic, often misdiagnosed disease characterized by painful, disproportionate fat accumulation in the extremities. Commonly mistaken for obesity or lymphedema, lipedema primarily affects women and has long been thought to be resistant to dietary intervention, a belief originating from its initial description by Allen and Hines at the Mayo Clinic in 1940. However, emerging research challenges this notion, revealing that individuals with lipedema often respond positively to therapeutic carbohydrate (CHO) reduction, particularly ketogenic diets (KD). Effective management of lipedema requires a comprehensive, holistic approach. Nutritional strategies should not only target symptom relief but also support overall health by considering physical comorbidities, mental and emotional well-being, and individual cultural and social factors. In this paper, we present an updated perspective on CHO-reduced dietary interventions for lipedema and propose a patient-centered framework to personalize nutrition plans for sustained success and improved quality of life.