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Lipedema is a chronic disease that mostly manifests in females as the abnormal distribution of subcutaneous adipose connective tissue, usually coupled with bruising, pain, and edema. Lipedema molecular pathophysiology is currently not clear, but several studies suggest that genetics and hormonal imbalance participate in lipedema pathogenesis. Women with lipedema present in some cases with elevated body mass index, and the appearance of obesity in addition to lipedema, where the obesity can cause serious health issues as in lipedema-free individuals with obesity, such as diabetes and cardiovascular disorders. Unlike obesity, lipedema tissue does not respond well to diet or physical exercise alone. Therefore, in this review we discuss the effect of various dietary supplements that, along with diet and physical exercise, cause fat burning and weight loss, and which could potentially be important in the treatment of lipedema. Indeed, an effective fat burner should convert stored fats into energy, mobilize and break down triglycerides in adipocytes, boost metabolism and inhibit lipogenesis. Common ingredients of fat burning supplements are green tea, caffeine, chromium, carnitine, and conjugated linoleic acid. The use of fat burners could act synergistically with a healthy diet and physical exercise for decreasing adipose tissue deposition in patients with lipedema and resolve related health issues. The effects of fat burners in human studies are sometimes contradictory, and further studies should test their effectiveness in treating lipedema.

Background and aims: Lipoedema is a little-known condition that is often misdiagnosed. Lipoedema presents with nodular to swollen areas that can lead to induration, nodular, uneven skin, as well as dimpling and skin flap formation, most commonly on the lower extremities, more rarely on the upper extremities The accumulation of adipose tissue results in characteristic symmetrical swelling of the extremities, ending above the ankles or wrists (cuff-sign). Primary pain phenomena include localized pain, tenderness, painful tightness, and pain on touch and pressure during activities. To get an insight in necessary self-management of pain and symptoms, a narrative review was conducted to identify requirement of self-management for coping with phenomena of pain in lipoedema and associated comorbidities. Methods: The narrative literature review includes international medical and guideline databases, as well as social media reports from affected persons. Analysis was performed using the content analysis method. Requirements of self-management, coping behaviour as well as individual case descriptions were searched. Results: 48 publications were identified. Guidelines and publications on guidelines accounted for a large proportion. Presentation of results outlines the range of requirements to manage pain with a bio-psycho-social pattern in the synthesis. Limiting spontaneous and pressure pain and secondary pain phenomena such as joint pain and mobility limitations are described. The prevention of chronification of pain in association with lipoedema has not yet been a direct aim in the therapeutic strategy. Conclusions: A knowledge gap regarding the incidence of pain syndrome and chronification shows major deficits of self-management strategies and implies further research needs.

In recent years, more attention is being paid to the hormonal aspect of lipoedema. There are suggestions that lipoedema patients may have particular imbalances or sensitivities with regard to oestrogens and/ or progesterone. This article examines the specifics of gluteofemoral fat storage during pregnancy: increased gluteofemoral storage with strong resistance to lipolysis. It then asks if hormonal dysregulation in lipoedema patients could result in a hormonal profile that mimics pregnancy. Such a profile may include high levels of oestrogens, progesterone, prolactin and relaxin, or any combination of the above. This pseudopregnancy hormonal profile would instruct the body to store gluteofemoral fat and strongly resist all attempts to mobilise it.

Lipedema patients suffer not only from visual stigma but also reduction in their quality of life through pain and performance loss in daily life. In clinical practice, it is still difficult to reliably diagnose the disease. This study aims to provide further insights into the characteristics of lipedema patients of all stages and provide a baseline prior to surgery for a surgical treatment evaluation by means of patient-reported outcome measures. METHODS: Patients completed a lipedema-specific questionnaire containing 50 items, the World Health Organization Quality of Life BREF (WHOQOL-BREF) and the Patient Health Questionnaire 9 (PHQ-9). The data were analyzed using SPSS statistics 27. Patients who had already received liposuction were excluded. RESULTS: Five hundred and eleven patients were included, of whom 337 completed the PHQ9 and 333 completed the WHOQOL-BREF questionnaires. The general characteristics of lipedema patients, especially the daily symptoms, are described. Previous observations, such as the frequent occurrence of hypothyroidism and the low rate of type 2 diabetes, were confirmed. Over 49% suffer from severe impairments in their jobs, whereby the disease shows a familial accumulation. The results of the WHOQOL-BREF and the PHQ-9 suggest a high level of mental stress. DISCUSSION: As surgical intervention in lipedema patients is gaining traction, its effects should be well-documented. Therefore, a comprehensive baseline needs to be established prior to surgical treatment. The psychological components are just as important as the inclusion of daily impairments.

Lipedema is a chronic, progressive disease of adipose tissue with unknown etiology. Based on the relevance of the stromal vascular fraction (SVF) cell population in lipedema, we performed a thorough characterization of subcutaneous adipose tissue, SVF isolated thereof and the sorted populations of endothelial cells (EC), pericytes and cultured adipose-derived stromal/stem cells (ASC) of early-stage lipedema patients. We employed histological and gene expression analysis and investigated the endothelial barrier by immunofluorescence and analysis of endothelial permeability in vitro. Although there were no significant differences in histological stainings, we found altered gene expression of factors relevant for local estrogen metabolism (aromatase), preadipocyte commitment (ZNF423) and immune cell infiltration (CD11c) in lipedema on the tissue level, as well as in distinct cellular subpopulations. Machine learning analysis of immunofluorescence images of CD31 and ZO-1 revealed a morphological difference in the cellular junctions of EC cultures derived from healthy and lipedema individuals. Furthermore, the secretome of lipedema-derived SVF cells was sufficient to significantly increase leakiness of healthy human primary EC, which was also reflected by decreased mRNA expression of VE-cadherin. Here, we showed for the first time that the secretome of SVF cells creates an environment that triggers endothelial barrier dysfunction in early-stage lipedema. Moreover, since alterations in gene expression were detected on the cellular and/or tissue level, the choice of sample material is of high importance in elucidating this complex disease.

Lipedema is a multifaceted chronic fat disorder characterized by the bilateral and disproportionate accumulation of fat predominantly in the lower body regions of females. Research strongly supports that estrogen factors likely contribute to the pathophysiology of this disease. We aim to help demonstrate this link by quantifying estrogen factor differences between women with and without lipedema. For time and lipedema adipose tissue conservation, the Protein Simple WES machine will be utilized in place of traditional western blotting. Here, we are interested in evaluating estrogen related factors, such as, but not limited to, estrogen receptors and enzymes involved in the successive conversions of cholesterol and androgens to estrogens in human subcutaneous adipose. Evaluation of these factors within adipose tissue, however, is novel for this instrument. Thus, we optimized tissue lysis and protein extraction for 11 proteins of interest. Antibodies and their working concentrations were determined based upon specific and distinguishable (signal-to-noise) peaks from electropherogram outputs across different tissue lysate concentrations. We found that overnight acetone precipitation proved to be the best procedure for extracting protein from lipid rich adipose tissue samples. Six of the eleven proteins were found to migrate to their expected molecular weights, however, five did not. For proteins that did not migrate as expected, overexpression lysates and empty vector controls were used to validate detection antibodies. Protein extract from subcutaneous adipose tissue and overexpression lysates were then combined to understand if migration was specifically altered by adipose tissue. From these results, we concluded that the lipid rich nature of adipose tissue in combination with the separation matrix designated for use with the WES were preventing the appropriate migration of some proteins rather than non-specific antibody binding or inappropriate preparation methods.

Background: The lymphatic contribution to the circulation is of paramount importance in regulating fluid homeostasis, immune cell trafficking/activation and lipid metabolism. In comparison to the blood vasculature, the impact of the lymphatics has been underappreciated, both in health and disease, likely due to a less well-delineated anatomy and function. Emerging data suggest that lymphatic dysfunction can be pivotal in the initiation and development of a variety of diseases across broad organ systems. Understanding the clinical associations between lymphatic dysfunction and non-lymphatic morbidity provides valuable evidence for future investigations and may foster the discovery of novel biomarkers and therapies. Methods: We retrospectively analysed the electronic medical records of 724 patients referred to the Stanford Center for Lymphatic and Venous Disorders. Patients with an established lymphatic diagnosis were assigned to groups of secondary lymphoedema, lipoedema or primary lymphovascular disease. Individuals found to have no lymphatic disorder were served as the non-lymphatic controls. The prevalence of comorbid conditions was enumerated. Pairwise cooccurrence pattern analyses, validated by Jaccard similarity tests, was utilised to investigate disease–disease interrelationships. Results: Comorbidity analyses underscored the expected relationship between the presence of secondary lymphoedema and those diseases that damage the lymphatics. Cardiovascular conditions were common in all lymphatic subgroups. Additionally, statistically significant alteration of disease–disease interrelationships was noted in all three lymphatic categories when compared to the control population.

Recommendations: 1.1 Evidence on the safety of liposuction for chronic lipoedema is inadequate but raises concerns of major adverse events such as fluid imbalance, fat embolism, deep vein thrombosis, and toxicity from local anaesthetic agents. Evidence on the efficacy is also inadequate, based mainly on retrospective studies with methodological limitations. Therefore, this procedure should only be used in the context of research. Find out what only in research means on the NICE interventional procedures guidance page. 1.2 Further research should report: • patient selection, including age, effects of hormonal changes (which should include effects seen during puberty and menopause) and the severity and site of disease • details of the number and duration of procedures, the liposuction technique used (including the type of anaesthesia and fluid balance during the procedure), and any procedure-related complications • long-term outcomes, including weight and body mass index changes • patient-reported outcomes, including quality of life. 1.3 Patient selection should be done by a multidisciplinary team, including clinicians with expertise in managing lipoedema. 1.4 The procedure should only be done in specialist centres by surgeons experienced in this procedure.

Attention has been drawn to the role of changes in visceral adipose tissue rather than subcutaneous adipose tissue in the relationship between adipokines and dysfunctional adipose tissue. Especially in lipedema in which subcutaneous adipose tissue is affected, information about adipokines is insufficient. In this study, it was aimed to investigate adiponectin, ghrelin, resistin and visfatin levels and their relationship with adipose tissue thickness in patients with lipedema. For this purpose, subcutaneous adipose tissue thickness was evaluated objectively by ultrasonography. A total of 19 female patients diagnosed with lipedema and 15 healthy women with no age difference were included in the study. Skin and subcutaneous adipose tissue thickness were measured ultrasonographically. Serum levels of adiponectin, ghrein, resistin and visfatin of all subjects were measured using sandwich ELISA protocol. In patients with lipedema, subcutaneous subcutaneous tissue thickness and total skin-subcutaneous thickness were significantly increased in the thigh and calf, excluding skin thickness in the thigh, compared to controls (P0.05). No significant correlation was found between adiponectin, ghrelin, resistin and visfatin and skin, subcutaneous and total thickness measurements by ultrasound in patients with lipedema and controls (P>0.05). Although not statistically significant, when examined in detail, positive or negative correlations were observed between the groups in the relationship between adipokines and ultrasound measurements. According to our findings, although no significant relationship was found between serum levels of adipokines and subcutaneous adipose tissue thickness, it is controversial that they are completely unrelated. Further studies in larger series will shed light on the relationship between adipokines and subcutaneous tissue thickness and the importance of ultrasonography. , Adipokinler ve disfonksiyonel yağ dokusu arasındaki ilişkide subkutan yağ dokusundan ziyade viseral yağ dokusundaki değişikliklerin rolüne dikkat çekilmiştir. Özellikle cilt altı yağ dokusunun etkilendiği lipödemde adipokinler hakkında bilgi yetersizdir. Bu çalışmada lipödemli hastalarda adiponektin, ghrelin, resistin ve visfatin düzeylerinin ve bunların yağ doku kalınlığı ile ilişkisinin araştırılması amaçlandı. Bu amaçla cilt altı yağ dokusu kalınlığı ultrasonografi ile objektif olarak değerlendirildi. Lipödem tanısı almış toplam 19 kadın hasta ve yaş farkı olmayan 15 sağlıklı kadın çalışmaya dahil edildi. Deri ve deri altı yağ dokusu kalınlıkları ultrasonografik olarak ölçüldü. Tüm deneklerin serum adiponektin, ghrein, resistin ve visfatin seviyeleri sandviç ELISA protokolü kullanılarak ölçüldü. Lipödemli hastalarda, uyluk ve baldırda subkutan subkutan doku kalınlığı ve toplam deri-subkutan kalınlığı kontrollere kıyasla, uyluktaki deri kalınlığı dışında önemli ölçüde arttı (P0.05). Lipödemli hastalarda ve kontrollerde ultrason ile adiponektin, ghrelin, resistin ve visfatin ile deri, deri altı ve toplam kalınlık ölçümleri arasında anlamlı bir ilişki bulunmadı (P>0.05). İstatistiksel olarak anlamlı olmasa da detaylı incelendiğinde adipokinler ve ultrason ölçümleri arasındaki ilişkide gruplar arasında pozitif veya negatif korelasyonlar gözlendi. Bulgularımıza göre, serum adipokin düzeyleri ile deri altı yağ dokusu kalınlığı arasında anlamlı bir ilişki bulunmamakla birlikte, tamamen ilgisiz oldukları tartışmalıdır. Daha geniş serilerde yapılacak çalışmalar adipokinlerin cilt altı doku kalınlığı ile ilişkisine ve ultrasonografinin önemine ışık tutacaktır.

Lipoedema has received increased attention in recent years. Overlaps with obesity sometimes make it difficult to differentiate. However, this is important for a differentiated targeted therapy. Definition and clinic Lipoedema is a painful, genetic, exces sive increase in adipose tissue on the extremities in women. This leads to a disproportion of the body. The first symptoms often manifest themselves in puberty, the course is usually progressive. Characteristic symptoms are pain at rest and pressure, tendency to hematoma, feelings of tension and swelling, rapid fatigue of the muscles and edema, which are inconsistent depending on the stage. 25–88 % of lipoedema patients suffer from obesity at the same time. Prevalence Depending on the study, 5–9.7 %, corresponding to 2–4 million women in Germany. Etiology Family disposition is obvious. Hormonal changes are trigger factors and suggest hormonal influences. In the tissue there is a slight chronic inflammation (silent inflammation), which explains the symptoms. Diagnosis The diagnosis is made clinically and must be distin guished from other fat distribution disorders. The BMI is not suitable. The waist circumference-size quotient (BCG = WHtR Waist to Height-Ratio) should be used. Therapy interdisciplinary therapeutic approach,which inaddi tion to conservative decongestion therapy, surgical therapy by liposuction also includes nutrition, exercise and psychotherapy.

Lipedema PubMed published article

El lipedema es un trastorno crónico que se presenta en mujeres durante la pubertad u otros momentos de cambios hormonales como en el embarazo o la menopausia.  Es caracterizado por una obesidad desproporcionada de las extremidades, especialmente en caderas y piernas, asociado a hematomas con mínimo trauma y dolor espontáneo o inducido por presión. Usualmente es mal diagnoticado e infratratado y suele confundirse con otras enfermedades como la obesidad y linfedema. Su causa aún se sigue estudiando, existen hipótesis sobre su origen poligenético regulado por los estrógenos, por el inicio de la enfermedad en etapas de cambio hormonal y debido a que se presenta mayormente en mujeres. Los tratamiento para el lipedema se basa en seis pilares: 1) Fisioterapia-ejercicios, 2) Terapia compresiva, 3) Control de peso, 4) Liposucción, 5) Terapia psicosocial-6) Automanejo.

Lipedema is a disabling disease characterized by symmetric enlargement of the lower and/or upper limbs due to deposits of subcutaneous fat, that is easily misdiagnosed. Lipedema can be primary or syndromic, and can be the main feature of phenotypically overlapping disorders. The aim of this study was to design a next-generation sequencing (NGS) panel to help in the diagnosis of lipedema by identifying genes specific for lipedema but also genes for overlapping diseases, and targets for tailored treatments. We developed an NGS gene panel consisting of 305 genes potentially associated with lipedema and putative overlapping diseases relevant to lipedema. The genomes of 162 Italian and American patients with lipedema were sequenced. Twenty-one deleterious variants, according to 3 out of 5 predictors, were detected in PLIN1, LIPE, ALDH18A1, PPARG, GHR, INSR, RYR1, NPC1, POMC, NR0B2, GCKR, PPARA in 17 patients. This extended NGS-based approach has identified a number of gene variants that may be important in the diagnosis of lipedema, that may affect the phenotypic presentation of lipedema or that may cause disorders that could be confused with lipedema. This tool may be important for the diagnosis and treatment of people with pathologic subcutaneous fat tissue accumulation.

BACKGROUND: Despite an increasing demand for surgical treatment of lipedema, the evidence for liposuction is still limited to five peer-reviewed publications. Little is known about the influence of disease stage, patient age, body mass index, or existing comorbidities on clinical outcomes. Considering the chronically progressive nature of lipedema, it was hypothesized that younger patients with lower body mass index and stage would report better results. METHODS: This retrospective, single-center, noncomparative study included lipedema patients who underwent liposuction between July of 2009 and July of 2019. After a minimum of 6 months since the last surgery, all patients completed a disease-related questionnaire. The primary endpoint was the need for complex decongestive therapy based on a composite score. Secondary endpoints were the severity of complaints (i.e., spontaneous pain, sensitivity to pressure, feeling of tension, bruising, impairment of body image) measured on a visual analogue scale. RESULTS: One hundred six patients underwent a total of 298 large-volume liposuctions (mean lipoaspirate, 6355 ± 2797 ml). After a median follow-up of 20 months (interquartile range, 10 to 42 months), a median complex decongestive therapy score reduction of 37.5 percent (interquartile range, 0 to 88.8 percent; p < 0.0001) was observed. An improvement in lipedema-associated symptoms was also observed (p < 0.0001). The percentage reduction in complex decongestive therapy scores was greater in patients with a body mass index less than or equal to 35 kg/m2; (compared to higher body mass index; p < 0.0001) and in stage I and II patients (compared to stage III patients; p = 0.0019). CONCLUSION: Liposuction reduces the severity of symptoms and the need for conservative treatment in lipedema patients, especially if it is performed in patients with a body mass index below 35 kg/m2; at an early stage of the disease. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Left ventricular (LV) twist is defined as the wringing motion of the LV around its long-axis during systole generated by rotation of the LV apex in a counterclockwise direction, as viewed from the apex, while the LV base moves in a clockwise direction. In several cases, the LV apex and base move in the same direction during ejection demonstrating a special condition called as LV 'rigid body rotation'. The present review aimed to summarize our knowledge about this rare but not fully understood entity demonstrating its theoretic pathophysiologic background, clinical significance, associated diseases, and reversibility based on available literature.

BACKGROUND: Lipedema often remains undiagnosed in patients with obesity, leading to mismanagement of treatment. Because of this, despite remarkable weight loss after bariatric surgery and decreases in hip and abdomen circumference, some patients show only small decreases in circumference of the extremities and report persistent limb pain. OBJECTIVE: The goal of this work is to raise awareness of lipedema coincident with obesity, mistakenly diagnosed as obesity alone, in order to ensure the correct diagnosis of the condition and to achieve better treatment outcomes for people with lipedema and coincident obesity. SETTING: CG Lympha Clinic, Cologne, and Ernst von Bergmann Clinic, Potsdam. METHODS: From clinical records, we identified 13 patients who were diagnosed with lipedema only after undergoing bariatric surgery. We describe the course of their pain before and after bariatric surgery, focusing on the long-term progression of symptoms accompanying the disease. RESULTS: Lipedema cannot be cured by bariatric surgery, and although the patients in this study lost an average of more than 50 kg of weight, they displayed no improvement in the pain symptoms typical of lipedema. CONCLUSIONS: Because of the different etiologies of lipedema and obesity, lipedema requires its own specific treatment. Patients suffering from obesity should always be assessed for pain and lipedema. If coincident lipedema is diagnosed, we suggest that bariatric surgery only be performed first if diet and exercise have failed, the patient's body mass index is >40 kg/m2, and the patient has been informed of the possible persistence of pain. Lipedema, like a coincident disease, must be additionally treated conservatively or preferably surgically. This optimized treatment may help to better manage patient expectations after weight loss.