Your search

Lipedema has long been misclassified as a cosmetic concern or a subtype of obesity, leading to delayed diagnosis and suboptimal surgical outcomes. Growing molecular, histopathologic, and imaging evidence supports lipedema as a systemic disorder involving adipose tissue, connective matrix, vascular–lymphatic integrity, and neuroimmune regulation. To integrate these findings into a clinically actionable model, we introduce the concept of Adipoconnective Fragility Syndrome (AFS), framing lipedema as a multisystem condition with direct implications for surgical planning and perioperative management.

Lipedema is a chronic and progressive adipose tissue disorder characterized by disproportionate fat accumulation, microvascular dysfunction, chronic inflammation, and progressive fibrosis. Despite its prevalence and significant impact on quality of life, current therapeutic approaches remain largely symptomatic and fail to address the underlying biological mechanisms of the disease. Emerging evidence suggests that lipedema should be understood as a multifactorial condition involving genetic susceptibility, endothelial alterations, immune dysregulation, and extracellular matrix remodeling. In this context, pharmacological strategies targeting these pathways have gained increasing attention. Metformin, through activation of AMP-activated protein kinase (AMPK), exerts antifibrotic and immunometabolic effects, including inhibition of TGF-β signaling, reduction of extracellular matrix deposition, and modulation of adipose tissue inflammation. In parallel, incretin-based therapies, particularly glucagon-like peptide-1 (GLP-1) receptor agonists and dual GLP-1/GIP agonists such as tirzepatide, have demonstrated pleiotropic effects that extend beyond weight reduction, including improvements in metabolic homeostasis, reduction of systemic inflammation, and enhancement of endothelial function. These therapies appear to act through complementary mechanisms, with metformin primarily targeting tissue remodeling and fibrosis, and incretin-based therapies exerting broader systemic effects on metabolism, inflammation, and vascular integrity. This review proposes a hypothesis-generating mechanistic framework, supporting a shift from weight-centric and symptomatic approaches toward disease-modifying strategies. Although current evidence in lipedema is largely indirect, the convergence of experimental and clinical data provides a strong rationale for further investigation. Future studies should focus on evaluating combined therapeutic approaches and identifying biomarkers that reflect fibrosis, inflammation, and microvascular dysfunction, with the aim of developing targeted and personalized treatments for this complex disorder.

Methods: Skin and subcutaneous adipose tissue (5-μm sections) were collected from one patient (hand, foot, back), fixed in formaldehyde, and stained for inflammatory markers (CD68, CD163) and endothelial cells (CD31). H&E and Masson’s trichrome staining were performed. Images were captured and manually quantified. Results: Cutaneous tissue from the hands and feet demonstrated increased microvascular density (CD31) with thickened walls, perivascular fibrosis, and macrophage infiltration (CD68, CD163). Macrophages were observed along the nerve fibers and outer nerve layers, consistent with localized nerve inflammation alongside vascular remodeling. Conclusion: This study demonstrates concurrent vascular remodeling and nerve-associated inflammation in lipedema adipose tissue of the hand and feet. These findings highlight that pain in lipedema involves both vascular and neurogenic inflammatory mechanisms, extending the understanding of lipedema pathology beyond the lower extremities.

Background/Objectives: Non-invasive radiofrequency (NIRF) therapy is increasingly used in physical rehabilitation. However, its efficacy across differ...

Lipedema is a lipodystrophic disease characterized primarily by a disproportionate increase in lower body subcutaneous fat. Although moderate weight loss decreases lower body fat mass in women with obesity and lipedema, it is possible that this decrease is due to a reduction in normal subcutaneous fat, rather than lipedema-affected fat. We evaluated the effect of moderate (11%) diet-induced weight loss on body fat mass and distribution, assessed by dual-energy X-ray absorptiometry and magnetic resonance imaging, in a 56-year-old woman with lipedema who was normal weight (body mass index: 23.9 kg/m2) at baseline. Approximately 85% of the decrease in body weight comprised body fat. The relative reduction in upper body fat (abdominal subcutaneous, arm and trunk fat) was similar to the relative reduction in lower body (total leg fat and thigh subcutaneous fat). Accordingly, weight loss did not change the proportion of total body fat comprising leg fat (44.8% and 45.1% before and after weight loss, respectively) or arm fat (9.1% and 9.6% before and after weight loss, respectively). These data suggest weight loss decreases lipedema-affected adipose tissue and demonstrate the therapeutic effect of weight loss on body composition in women with lipedema even if they are normal weight.

BACKGROUND: Lipedema is a chronic condition characterized by abnormal fat accumulation, primarily in the lower extremities, affecting mostly women. Despite improvements in diagnosis and treatment, lipedema is often misdiagnosed as obesity or lymphedema. Patients with obesity and lipedema propose a distinct clinical challenge in treating both diseases. Improved recognition and understanding are necessary to enhance diagnosis and treatment outcomes. PURPOSE OF THIS REVIEW: Lipedema is thought to be hormonally driven, often manifesting during puberty, pregnancy, or menopause. It presents as disproportionate fat accumulation in the lower body, often with microvascular changes. Misdiagnosis as obesity or lymphedema leads to ineffective treatments like weight loss programs and bariatric surgery. Effective management involves both conservative and surgical approaches, as well as a tailored strategy for patients with both lipedema and obesity. The focus of this review is to summarize the current literature addressing adequate treatment regimens for patients with both diseases and based on the literature we propose a treatment protocol. CONCLUSION: Patients with concurrent lipedema and obesity propose a distinct clinical challenge, in which early recognition can benefit adequate treatment. A combination of conservative measures and surgical options, particularly liposuction and/or bariatric and metabolic surgery, can be beneficial in treating patients with both diseases. However future research is needed to assess the effect of different treat regimens.

Lipedema is a chronic, progressive adipose tissue disorder characterized by disproportionate subcutaneous fat accumulation, pain, edema, and resistanc...

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.

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.

DiVA portal is a finding tool for research publications and student theses written at the following universities and research institutions.

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 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.

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.