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Adipose tissue, or “fat”, has become synonymous with obesity. The public discourse frames a desire to reduce or even banish this tissue at almost every turn, with reasons ranging from aesthetics to health improvements. During decades of research into the development of adipose tissue-reducing interventions, there has also been an increasing acknowledgement and understanding of the physiological necessity for adipose tissue. Functional adipose tissue contributes to overall health due to its role in an incredibly diverse array of processes. For that reason, dysfunction in this tissue continues to be linked to a wide variety of pathologies, from infection to cancer and everything in between. In this book, we gather expert input from those currently expanding this field to provide insight into the importance of adipose tissue.

INTRODUCTION: Lipedema is a chronic and progressive disease that predominantly affects women, characterized by a disproportionate increase in subcutaneous adipose tissue (AT), particularly in the lower limbs. It is associated with significant physical disability, chronic pain, thromboembolism, and psychosocial distress. Despite its profound impact on women's health and quality of life, lipedema remains underrecognized and insufficiently studied, with an estimated prevalence of approximately 10% among women worldwide. Although the exact etiology of lipedema remains unclear, emerging evidence suggests a multifactorial origin involving genetic predisposition, hormonal influences, and vascular dysfunction-all contributing to its development and progression. Current therapeutic options provide only partial symptom relief and remain noncurative, highlighting the urgent need for expanded research and improved management strategies. METHODS: A systematic review was conducted to assess the current understanding of lipedema pathophysiology and current treatment options. Research articles were sourced from PubMed, Web of Science, ScienceDirect, and Scopus databases. Over 100 studies were incorporated. RESULTS: This review provides a comprehensive overview of lipedema, encompassing its clinical features, pathophysiological mechanisms, diagnostic challenges, and current treatment modalities. Additionally, the review discusses whether the molecular and metabolic differences between abdominal and femoral AT depots mirror those observed in classical obesity. CONCLUSIONS: Multidisciplinary, research-informed care is essential for managing lipedema, combining conservative therapies, tailored exercise, and liposuction for advanced cases. More research to better understand the underlying pathophysiology is critical to developing targeted treatments, improving diagnostic accuracy, and informing standardized, evidence-based care.

Objectives: This study aimed to examine the effects of a multimodal exercise program on edema, pain, exercise capacity, lower extremity muscle strength, and function in patients with lipedema.Methods: The patients diagnosed with lipedema were randomly assigned to either the exercise (n: 11) or control (n: 11) groups. The exercise group participated in supervised group exercises focusing on aerobic and strengthening, twice a week for 6 weeks. The control group received training on physical activity additionally lipedema management. Sociodemographic and clinical characteristics were recorded. Edema (circumference measurements and local tissue water-LTW%), pain intensity (Visual Analogue Scale-VAS) and pressure pain threshold (Algometer), functional exercise capacity (Six minute walk test-6MWT), lower extremity muscle strength (Handheld dynamometer), lower extremity muscle strength/endurance (Sit-to-stand test) and lower extremity function (Lower Extremity Functional Scale-LEFS) were evaluated.Results: In the exercise group, significant reductions in pain during rest, activity, and nighttime, 6MWT distance, quadriceps and hip muscle strength, lower extremity strength/endurance, and function were observed (p < .05). When comparing the groups, no significant differences were found (p > .05); however, clinically, there were differences in limb volumes, pain reduction, muscle strength, and functional improvements, with medium to large effect sizes.Conclusion: The main findings of this study highlight the benefits of structured multimodal exercises for patients with lipedema to improve pain, limb volumes, exercise capacity, lower extremity muscle strength, endurance, and functionality.Clinical trials number: NCT06811961.

Lipedema is an adipose tissue disorder that principally affects women and is frequently misidentified as obesity or lymphedema. There have been relatively few studies that have precisely defined the pathogenesis, epidemiology, and treatment approaches for lipedema. However, successfully recognizing lipedema as a distinct condition is important for proper management. This review aimed to examine the existing literature on the epidemiology, pathogenesis, clinical presentation, differential diagnosis, and treatments for lipedema. The current research indicates that lipedema appears to be a clinical entity related to genetic factors and fat distribution, although distinct from lymphedema and obesity. Some available treatments include complex decongestive physiotherapy, liposuction, and laser-assisted lipolysis. The management of lipedema is complex and differs from that of lymphedema. Further high-quality randomized controlled trials are urgently needed to continue advancing our understanding of this often neglected disease and exploring optimal medical and surgical treatment regimens tailored specifically for lipedema patients. In summary, despite frequent misdiagnosis, enhanced recognition, and research into customized therapeutic strategies for this poorly characterized but likely underdiagnosed disorder represent promising steps forward. Level of evidence  N/A.

Background: Pain is a prevalent symptom in patients with lipedema predominantly impacting the lower extremities. This study aimed to evaluate the relationship between 25-hydroxyvitamin D [25(OH)D] and vitamin B12 levels and neuropathic pain (NP) in patients diagnosed with lipedema. Methods and Results: A total of 243 patients with lipedema who had 25(OH)D and B12 levels measured in the past 6 months were included in this study. Participants were divided into two groups: Group 1 (N = 78) with NP scores ≥13 and Group 2 (N = 165) with NP scores <13. The Turkish version of the painDETECT questionnaire was used to assess the patients' NP symptoms. Pain levels were measured using the Visual Analog Scale (VAS) and pain threshold through algometric measurement. Group 1 had significantly higher palpation and spontaneous VAS scores, and pain threshold through algometric measurements than Group 2 (p < 0.05). No statistically significant difference was found between the groups regarding vitamin D levels being below 30 ng/mL or vitamin B12 levels being below 400 pg/mL (p > 0.05). Conclusions: No association was found between NP and 25(OH)D or B12 levels in patients with lipedema.

Lipedema diagnosis is heavily reliant on patient history. Various objective assessments have been suggested; however, a standardized measurement process is lacking. A systematic review was undertaken to identify which imaging and measurement tools are used in lipedema quantification and to review their protocols. Six databases were searched with two reviewers screening citations for inclusion. Full peer-reviewed publications that included defined lipedema diagnosis criteria, no male cases within comparative cohorts, and used an imaging or measurement tool to quantify lipedema were included. Twenty studies met the inclusion criteria using 13 different tools to quantify individual physical lipedema characteristics to either enable differential diagnosis, and/or quantify treatment effect: tape measure, perometry, durometry, tonometry, bioimpedance spectroscopy, tissue di-electric constant, ultrasound, Dual-Energy X-ray Absorptiometry, magnetic resonance imaging (MRI), noncontrast MRI lymphangiography, Indocyanine green lymphography, lymphoscintigraphy, and dynamic lymphangiography. Eight imaging and five measurement tools assessed lymphatic transport disturbances (n = 8), limb size/volume (n = 4), adipose tissue thickness/mass/volume (n = 3), and tissue fluid presence (n = 2). Multiple tools were only used in studies completed in 2020 or later. A lack of consistency exists in tool protocols, measurement locations, and outcome analysis. Limited reporting of clinimetrics with data derived from small cohorts and heterogenous populations impacted the ability to recommend tools for clinical practice and research. Various tools were used for objective lipedema assessment; however, consistency in approach was lacking. Further investigations are required to establish the validity and reliability of measurement and imaging tools, protocols, measurement points, and outcome reporting/interpretation to quantify the physical attributes of lipedema.

OBJECTIVES: To evaluate the presence of lipedema and lipedema-related factors in fibromyalgia patients. METHODS: The study included 100 female patients over the age of 18 who met the fibromyalgia diagnostic criteria. The patients were evaluated for the presence/stages of lipedema. The body mass index (BMI), waist-hip ratio, waist-height ratio, and presence of hematoma tendency/telangiectasias were recorded. Patients were asked to mark the severity of their pain (widespread/on lipedema) on a 10 cm visual analog scale (VAS). The ACR 2016 Fibromyalgia Diagnostic Criteria, The Beck Depression Inventory (BDI), and The Revised Fibromyalgia Impact Questionnaire were applied. RESULTS: Lipedema was observed in 50% of the patients (58% Stage 1 lipedema). In the lipedema group, age, duration of fibromyalgia diagnosis, hematoma tendency/presence of telangiectasias (for all; p < .001), menopausal status (p = .004), BDI score (p = .04), BMI (p = .02), history of medication for fibromyalgia (p = .01) were higher, and age at menarche (p = .01) was lower. Lipedema stage was moderately positively correlated with BMI, number of pregnancies (for both; r:0.53 p < .001) and waist-height ratio (r:0.43 p:0.002), while VAS-lipedema pain intensity was strongly positively correlated with VAS-widespread pain intensity (r:0.62 p < .001), and moderately positively correlated with symptom severity score (r:0.55 p < .001), BMI (r:0.54 p < .001), and fibromyalgia severity score (r:0.51 p < .001). Long fibromyalgia diagnosis time (p: 0.005), and low age at menarche (p: 0.05) were significant risk factors for the presence of lipedema. CONCLUSIONS: Lipedema is common in fibromyalgia patients. Long fibromyalgia diagnosis time and low age at menarche are significant risk factors for the presence of lipedema.

Lipedema, historically underrecognized, has recently gained attention due to advancements in research and growing public awareness. The Brazilian Consensus Statement on Lipedema, developed by the Brazilian Society of Angiology and Vascular Surgery, aims to establish clear recommendations for the diagnosis, treatment, and management of lipedema. Using the Delphi methodology, experts elaborated 90 statements about lipedema, which were then evaluated by a panel of 113 professionals. The statements were analyzed using SurveyMonkey, with a 75% agreement threshold required for their inclusion in the consensus statement. Most statements achieved significant consensus, with only 9 topics requiring further investigation. This consensus statement highlights the complexity of lipedema, the effectiveness of conservative treatment over surgery, the need for multidisciplinary approaches, and the importance of awareness to reduce underdiagnosis and stigma. It also underscores the ongoing need for research to develop more effective management strategies.

The Ketogenic Diet (KD) is currently the most widely studied nutritional approach for patients with lipedema, although its use may cause important drawbacks especially in case of comorbidities. A Modified Mediterranean Diet (MMed) is more easily adaptable, better tolerated, and can be temporarily replaced by a ketogenic diet for a short period of time if necessary using a sort of "sandwich" approach. We report 10 clinical cases with lipedema and comorbidities subjected to a hypocaloric MMed for 6 months. All patients were properly assessed by anthropometric measurements and body composition before and at the end of nutritional treatment. Only 2 patients needed a short period of KD due to poor response to MMed. At the end of 6-month follow-up, patients showed weight loss with reduction in body circumferences and improvement in body composition. In the two cases where it was necessary to resort to a period of KD, good results were achieved allowing a return to the MMed for the maintenance. In patients suffering from lipedema with associated comorbidities and concomitant pharmacological treatments, the use of MMed as first line treatment allows achievement of better metabolic balance, greater compliance, and improved body composition.

Lipoedema is a chronic and painful fat disorder that occurs almost exclusively in women. It mainly affects the legs and sometimes the arms. The condition not only causes physical complaints but also has a major impact on daily functioning and quality of life. Despite this, lipoedema is still poorly understood and appropriate care is often lacking. In this dissertation, we reviewed the existing literature on the functioning of people with lipoedema. In addition, we explored how they experience living with the condition, the challenges they face in managing it, and how healthcare professionals can provide better support. The studies show that lipoedema is more than meets the eye. Earlier research mainly focused on the physical aspects, while psychosocial issues such as shame, stigmatisation, and reduced social participation are equally important. Participants emphasised the need for personal guidance, access to specialised care, and reliable, evidence-based information. To address these needs, we developed a new self-management intervention: SELF-MANAGING your lipoedema. This programme helps people cope more effectively with their condition, take control of daily life, and set achievable goals together with their healthcare professionals. This dissertation highlights that good care for people with lipoedema must go beyond symptom management. A holistic approach is needed, alongside better knowledge and training for healthcare professionals, and policies that promote collaboration across disciplines. Such improvements can truly enhance the quality of life of those living with lipoedema.

BACKGROUND: The etiology of lipoedema remains unclear, making diagnosis and treatment challenging. Current treatment primarily consists of general lifestyle recommendations, with effective self-management being essential for integrating these recommendations into daily life. However, no self-management interventions currently address the unique needs of people with lipoedema. This study aimed to develop an evidence-based, theory-informed intervention to enhance self-management in people with lipoedema using the Intervention Mapping (IM) approach. METHODS: Following the first four steps of the IM approach, this study used a participatory methodology involving stakeholders, empirical data, and theory. Steps included: 1) needs assessment; 2) identification of outcomes, performance objectives, and change objectives; 3) selection of behavioural change methods; and 4) development of program components. RESULTS: The resulting intervention includes a program for people with lipoedema and a training program for healthcare professionals (HCPs). The intervention aims to empower patients to engage in self-management and equip HCPs to provide effective support. Key determinants targeted include self-efficacy, self-regulation skills, knowledge, attitudes, and social facilitation. The program for people with lipoedema consists of seven themes aligned with self-management behaviours and is delivered through 19 sessions: seven one-on-one sessions, one session involving supportive individuals, and 11 group sessions. The program for HCPs is delivered through six group sessions, each focusing on the core skills HCPs need to effectively deliver self-management support to their patients. CONCLUSION: The IM approach effectively guided a systematic, transparent, and reproducible development process. Grounded in established theories and behavioural change methods, the intervention provides a strong foundation for implementation and evaluation among people with lipoedema. The fifth and sixth steps of IM are considered future priorities.

PURPOSE: To describe and analyse experiences of living with lipedema. Methods: Individual, semi-structured interviews with a purposive sample of 12 women diagnosed with lipedema and analysed by qualitative content analysis utilizing an inductive approach. RESULTS: The overarching theme, "An uncertain uphill battle against a divergent body and societal ignorance", covers the experiences of living with lipedema and is based on five categories; "Captivated by a disintegrating body", "Face the impairments of a chronic condition", "Experience social exclusion", "Need emotional support to go on" and "Mull over an insecure future". The women felt entrapped within their bodies and experienced social exclusion due to the chronic symptoms and the progressive body shape alteration caused by their illness. Having experienced deficient information on the illness, varying support from other people, and a deteriorating economic situation, the women face an uncertain future. CONCLUSIONS: Symptoms and restrictions caused by lipedema affect women's livelihood and future, as there are no indications for disease improvement. Preventive work aimed at reducing health deterioration should be a priority. More research is needed to raise healthcare awareness regarding difficulties experienced by patients with lipedema.

BACKGROUND: Ketosis seems to attenuate, or prevent, the rise in both ghrelin concentrations and subjective hunger ratings that follow weight loss. However, most of the previous studies have employed very-low energy diets (VLED) and are therefore limited in terms of generalizability. OBJECTIVES: To compare changes in ghrelin plasma concentrations after a low-carbohydrate (LCD) versus an isocaloric low-fat low energy diet (LED) in females with lipedema. Secondary objectives were to determine potential differences between diets in changes in satiety hormones, and subjective ratings of appetite. METHODS: Females with obesity and lipedema were randomized to either an LCD (75 g carbohydrates) or low-fat diet (180 g carbohydrates) for 8 weeks. Plasma concentrations of ghrelin, peptide YY, cholecystokinin (CCK), and glucagon-like peptide 1 (GLP-1), and subjective ratings of appetite were measured in the fasting and postprandial states, pre and post intervention. RESULTS: 55 females (30 in LCD) were included (age 47.9 ± 11.3 years, BMI 36.8 ± 5.1 kg/m2). Both LCD and low-fat groups lost weight (10.3 %, P < 0.001 and 7.3 %, P < 0.001, respectively), but the LCD lost significantly more. No within or between groups differences were found for ghrelin in the fasting state. A reduction in postprandial (tAUC) ghrelin was seen only in the LCD group (P = 0.002), and this change was significantly different from the low-fat group (P = 0.046). The LCD group also reported an increase in postprandial (both iAUC and tAUC) fullness ratings (P = 0.035 and P = 0.005, respectively), but this was not significantly different from the low-fat group (P = 0.703 and P = 0.365, respectively), despite the latter experiencing no change (P = 0.127 and P = 0.152, respectively). Conversely, only the low-fat group reported increased hunger in fasting (P = 0.046), but changes were not significantly different from the LCD group (P = 0.711). A decrease in postprandial (both tAUC and iAUC) CCK was observed in both LCD and low-fat diet groups (P ≤ 0.005 for all). CONCLUSION: Despite no changes in fasting ghrelin concentrations in either of the diet groups, a reduction in postprandial ghrelin and increased fullness was seen in the LCD group. These favorable changes in appetite in the LCD group might have contributed to the greater weight loss observed in this group. CLINICAL TRIAL REGISTRATION: NCT04632810, Effect of Ketosis on Pain and Quality of Life in Patients With Lipedema (Lipodiet).

BACKGROUND: Lipedema is a disease typically affecting women with a symmetrical, painful fat distribution disorder, which is hypothesized to be caused by impaired adipogenesis, inflammation, and extracellular matrix remodeling, leading to fibrosis and the development of edema in lipedema subcutaneous adipose tissue. The pathogenesis and molecular processes leading to lipedema have not yet been clarified. METHODS: A whole transcriptome analysis of subcutaneous tissue of lipedema stages I (n = 12), II (n = 9), and III (n = 8) compared with hypertrophied subcutaneous tissue (n = 4) was performed. Further data about hormonal substitution and body morphology were collected. The study is registered at ClinicalTrials.gov (NCT05861583). RESULTS: We identified several differentially expressed genes involved in mechanisms leading to the development of lipedema. Some genes, such as PRKG2, MEDAG, CSF1R, BICC1, ERBB4, and ACP5, are involved in adipogenesis, regulating the development of mature adipocytes from mesenchymal stem cells. Other genes, such as MAFB, C1Q, C2, CD68, CD209, CD163, CD84, BCAT1, and TREM2, are predicted to be involved in lipid accumulation, hypertrophy, and the inflammation process. Further genes such as SHTN1, SCN7A, and SCL12A2 are predicted to be involved in the regulation and transmission of pain. CONCLUSIONS: In summary, the pathogenesis and development of lipedema might be caused by alterations in adipogenesis, inflammation, and extracellular matrix remodeling, leading to fibrosis and the formation of edema resulting in this painful disease. These processes differ from hypertrophied adipose tissue and may therefore play a main role in the formation of lipedema.

Lipedema is a chronic disorder affecting women with a 10% incidence worldwide. It is often confused with obesity. This study was undertaken to study microRNAs in lipedema tissue assessed by direct hybridization using the robust n-counter flex DX CE-IVD platform. The mean age of the subjects participating in the study was 40.29 (±12.17). The mean body weight and BMI were 67.37 (±10.02) and 25.75 (±4.10), respectively. The lipedema stages included were I and II. The differential expressed human (hsa)-miRNAs were determined according to a log2 fold-change (LFC) of 0.5 and p value < 0.05. To these, increased expression of hsa-let-7g-5p was evident, as well as reduced levels of hsa-miR-371a-5p, -4454+7975, -365a+b-3p, -205-5p, -196a-5p, -4488, -2116-5p, -141-3p, -208a-3p, -302b-3p, 374a-5p, and -1297. Then, several bioinformatics tools were used to analyze microarray data focusing on validated target genes in silico. KEGG and Gene Ontology (GO) pathway enrichment analysis was conducted. Furthermore, the protein-protein interaction and co-expression network were analyzed using STRING and Cytoscape, respectively. The most upregulated miRNA mainly affected genes related to cell cycle, oocyte meiosis, and inflammatory bowel disease. The downregulated microRNAs were related to endocrine resistance, insulin resistance, hypersensitivity to AGE-RAGEs, and focal adhesion. Finally, we validated by RT-PCR the upregulated hsa-let-7g-5p and two down-regulated ones, hsa-miR-205-5p and hsa-miR-302b-3p, confirming microarray results. In addition, three mRNA target miRNAs were monitored, SMAD2, the target of the hsa-let-7g-5p, and ESR1 and VEGFA, the target of hsa-miR-205-5p and hsa-miR-302b-3p, respectively. Our results open a new direction for comprehending biochemical mechanisms related with the pathogenesis of lipedema, shedding light on this intricate pathophysiological condition that could bring to light possible biomarkers in the future.

The treatment of lipedema remains challenging, largely due to widespread misconceptions. Selecting the appropriate treatment method necessitates the use of accurate outcome measures. This study aims to evaluate the effectiveness of compression therapy combined with exercises versus exercises alone in lipedema patients using various outcome measures. Twenty-four women with lipedema were divided into two equal groups: one group received compression therapy plus exercises while the other group performed exercises only. The effectiveness of the treatment was assessed before and after the intervention using several measures: an SF-36 questionnaire, a symptom severity survey, circumference (via 3D scanning), and body composition analysis. Significant improvements were observed in the SF-36 Physical Functioning and SF-36 Energy/Fatigue scores among participants in the compression group. Additionally, there was a reduction in the heaviness of extremities, the disproportion between the trunk and limbs, and the level of swelling in the compression therapy. Circumferences decreased in both groups. Although more circumferences were significantly reduced in the compression group, the reduction at the point above the knee was greater in the non-compression group. Compression therapy is an effective treatment for lipedema. Various measures, such as quality-of-life questionnaires and symptom severity surveys, can be used as valuable tools for assessing the effectiveness of lipedema treatment.

Background: Lipedema is a disease characterized by an increase in extracellular fluid. In these patients, the increase in the amount of extracellular fluid may accelerate the progression of the disease. The aim of this study is to examine the effect of complex decongestive therapy (CDT) on intracellular/extracellular fluid balance. Methods and Results: Twenty-two female patients diagnosed with lipedema by a specialist lymphologist were included in the study. Patients were subjected to complex decongestive therapy and pneumatic compression therapy 6 days a week for 1 month. Extracellular and intracellular fluid volumes were assessed using bioimpedance spectroscopy before and after the treatment. A decrease in intracellular (p = 0.010) and extracellular (p = 0.002) fluid volumes was observed after the treatment. Conclusion: There is no completely curative treatment method for lipedema. Current treatments aim to slow down the progression of the disease. CDT is considered effective in reducing intracellular and extracellular fluid volume in lipedema patients. Therefore, it is thought to be effective in slowing down the progression of the disease.