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The metabolic consequences of obesity arise from local inflammation within expanding adipose tissue. In pre-clinical studies targeting various inflammatory factors, systemic metabolism can be improved through reduced adipose inflammation. Lymphatic vessels are a critical regulator of inflammation through roles in fluid and macromolecule transport and immune cell trafficking and immunomodulation. Lymphangiogenesis, the expansion of the lymphatic network, is often a necessary step in restoring tissue homeostasis. Using Adipo-VD mice, a model of adipocyte-specific, inducible overexpression of the potent lymphangiogenic factor vascular endothelial growth factor-D (VEGF-D), we previously identified that dense de novo adipose lymphatics reduced immune accumulation and improved glucose homeostasis in obesity. On chow diet, however, Adipo-VD mice demonstrated increased adipose tissue immune cells, fibrosis, and inflammation. Here, we characterize the time course of resident macrophage accumulation and lymphangiogenesis in male and female Adipo-VD mice fed chow and high fat diets, examining multiple adipose depots over 4 months. We find that macrophage infiltration occurs early, but resolves with concurrent lymphatic expansion that begins robustly after 1 month of VEGF-D overexpression in white adipose tissue. In obesity, female Adipo-VD mice exhibit reduced lymphangiogenesis and maintain a more glycolytic metabolism compared to Adipo-VD males and their littermates. Adipose lymphatic structures appear to expand by a lymphvasculogenic mechanism involving lymphatic endothelial cell proliferation and organization with a cell source we that failed to identify; hematopoietic cells afford minimal structural contribution. While a net positive effect occurs in Adipo-VD mice, adipose tissue lymphangiogenesis demonstrates a dichotomous, and time-dependent, inflammatory tissue remodeling response.

Lipomas are defined as a common subcutaneous tumor composed of adipose (fat) cells, often encapsulated by a thin layer of fibrous tissue.[1] In fact, these are the frequently encountered neoplasms by the clinicians. [2] Clinically, they often present in the body's cephalic part, specifically in the head, neck, shoulders, and backs of patients. However, they can less commonly be seen elsewhere, for example, the thighs. The tumors typically lie in the subcutaneous tissues of patients. The masses are often benign, and while the age of onset can vary. There is usually no reason for treatment. They pose no threat to the patient unless they are uncomfortable due to being located on joints or rapidly growing, which is uncommon, as the typical lipoma growth is slow. Lipomas can sometimes, though rare, be associated with certain disorders such as multiple hereditary lipomatosis, Gardner syndrome, adiposis dolorosa, and Madelung disease.[3] [4] Some unconventional forms of lipomas include the following: angiolipoma, chondroid lipoma, lipoblastoma, myolipoma, pleomorphic lipoma/spindle cell lipoma, intramuscular and intermuscular lipoma, lipomatosis of nerve, lipoma of the tendon sheath and joint, lipoma arborescens, multiple symmetric lipomatosis, diffuse lipomatosis, adiposis dolorosa, and hibernoma.

Purpose To quantify chemical exchange saturation transfer contrast in upper extremities of participants with lymphedema before and after standardized lymphatic mobilization therapy using correction procedures for B0 and B1 heterogeneity, and T1 relaxation. Methods Females with (n = 12) and without (n = 17) breast cancer treatment-related lymphedema (BCRL) matched for age and body mass index were scanned at 3.0T MRI. B1 efficiency and T1 were calculated in series with chemical exchange saturation transfer in bilateral axilla (B1 amplitude = 2µT, Δω = ±5.5 ppm, slices = 9, spatial resolution = 1.8 × 1.47 × 5.5 mm3). B1 dispersion measurements (B1 = 1-3 µT; increment = 0.5 µT) were performed in controls (n = 6 arms in 3 subjects). BCRL participants were scanned pre- and post-manual lymphatic drainage (MLD) therapy. Chemical exchange saturation transfer amide proton transfer (APT) and nuclear Overhauser effect (NOE) metrics corrected for B1 efficiency were calculated, including proton transfer ratio (PTR'), magnetization transfer ratio asymmetry , and apparent exchange-dependent relaxation (AREX'). Nonparametric tests were used to evaluate relationships between metrics in BCRL participants pre- versus post-MLD (two-sided P < 0.05 required for significance). Results B1 dispersion experiments showed nonlinear dependence of Z-values on B1 efficiency in the upper extremities; PTR' showed < 1% mean fractional difference between subject-specific and group-level correction procedures. PTR'APT significantly correlated with T1 (Spearman's rho = 0.57, P < 0.001) and body mass index (Spearman's rho = −0.37, P = 0.029) in controls and with lymphedema stage (Spearman's rho = 0.48, P = 0.017) in BCRL participants. Following MLD therapy, PTR'APT significantly increased in the affected arm of BCRL participants (pre- vs. post-MLD: 0.41 ± 0.05 vs. 0.43 ± 0.03, P = 0.02), consistent with treatment effects from mobilized lymphatic fluid. Conclusion Chemical exchange saturation transfer metrics, following appropriate correction procedures, respond to lymphatic mobilization therapies and may have potential for evaluating treatments in participants with secondary lymphedema.

Lipedema is a chronic and progressive disease of adipose tissue caused by abnormal fat accumulation in subcutaneous tissue. Although there is no known cure for lipedema, possible complications can be prevented with conservative and surgical treatments. One of the conservative treatment options is physiotherapy and rehabilitation (PR). When the literature is examined, few studies focusing on the efficacy of PR were found for this patient group. The purpose of this review is to provide a better understanding of the effectiveness of PR applications by compiling existing studies. A bibliographic PubMed search was performed for published studies regarding PR in lipedema management in June 2019 including the last 58 years (1951-2019). Articles were chosen by reading the abstracts and subsequently data were analyzed by reading the entire text through full-text resources. A total of 15 studies met inclusion criteria. Results document how lipedema patients are benefited by PR and the effectiveness of different types of PR programs. The current review also showed that complex decongestive physiotherapy, gait training, hydrotherapy, aerobic exercise, and resistance exercise training each have value in the management of lipedema. The effects of PR for the treatment of lipedema are variable among studies, although overall PR seems to be effective in lipedema management. Although physiotherapy applications have a potentially important role in the management of lipedema, they should be used in combination with other treatment modalities. More studies with higher quality are needed to fully demonstrate the effect and efficacy of PR in lipedema patients.

Lipedema can cause chronic pain and increases patients’ risk for conditions such as lymphedema and venous disease. This author explores how lipedema affects the body, why its effects are disproportionate in the lower body, and how to diagnose and manage the condition.

Obesity is a leading cause of cardiovascular diseases and cancer. Body mass is regulated by the balance between energy uptake and energy expenditure. The etiology of obesity is determined by multiple factors including genetics, nutrient absorption, and inflammation. Lymphatic vasculature is starting to be appreciated as a critical modulator of metabolism and obesity. The primary function of lymphatic vasculature is to maintain interstitial fluid homeostasis. Lymphatic vessels absorb fluids that extravasate from blood vessels and return them to blood circulation. In addition, lymphatic vessels absorb digested lipids from the intestine and regulate inflammation. Hence, lymphatic vessels could be an exciting target for treating obesity. In this article, we will review our current understanding regarding the relationship between lymphatic vasculature and obesity, and highlight some open questions.

Lipedema is a chronic, progressive, painful, increased deposition subcutaneous fat tissue in women with a clear disproportion between the trunk and extremities. Lipedema offen lead to oedema, which are worsened by orthostasis, and hematoma after minor injury. The pathogenesis is unknown and no curative treatment is available. Conservative therapy consisting of lymphatic drainage and compression stockings is often recommended, but is only effective against the edema component. Some patients show a short-term improvement when treated in this way. Permanent reduction of the pathological subcutaneous fat on the legs and arms has become possible by employing advanced liposuction techniques using microcannula technology in local tumescent anaesthesia.

Genetic or acquired defects of the lymphatic vasculature often result in disfiguring, disabling, and, occasionally, life-threatening clinical consequences. Advanced forms of lymphedema are readily diagnosed clinically, but more subtle presentations often require invasive imaging or other technologies for a conclusive diagnosis. On the other hand, lipedema, a chronic lymphatic microvascular disease with pathological accumulation of subcutaneous adipose tissue, is often misdiagnosed as obesity or lymphedema; currently there are no biomarkers or imaging criteria available for a conclusive diagnosis. Recent evidence suggests that otherwise-asymptomatic defective lymphatic vasculature likely contributes to an array of other pathologies, including obesity, inflammatory bowel disease, and neurological disorders. Accordingly, identification of biomarkers of lymphatic malfunction will provide a valuable resource for the diagnosis and clinical differentiation of lymphedema, lipedema, obesity, and other potential lymphatic pathologies. In this paper, we profiled and compared blood plasma exosomes isolated from mouse models and from human subjects with and without symptomatic lymphatic pathologies. We identified platelet factor 4 (PF4/CXCL4) as a biomarker that could be used to diagnose lymphatic vasculature dysfunction. Furthermore, we determined that PF4 levels in circulating blood plasma exosomes were also elevated in patients with lipedema, supporting current claims arguing that at least some of the underlying attributes of this disease are also the consequence of lymphatic defects., , Characterization of plasma-circulating exosomes from mouse models and patients with lymphatic dysfunction indicate that PF4 is a promising biomarker for the diagnosis of lymphatic disorders.

In recent years stem cell research has become increasingly important for regenerativemedicine and tissue engineering. The isolation of stem cells from adipose tissue evades ethicalconcerns with which embryonic stem cells and induces pluripotent stem cells (iPS) are afflicted,because of its declaration as clinical waste material. Tumescent liposuction is a minimallyinvasive procedure providing high amounts of adipose tissue rich in therapeutically relevantcells within a short time. The isolated stromal vascular fraction (SVF) and the adipose derivedstromal/stem cells (ASC) contained therein show a high regenerative potential and have beensuccessfully used in many clinical studies. Maintaining SVF cells in their natural environmentand therefore providing the maximum possible regenerative potential of adipose tissue-derivedcells is a prerequisite for successful autologous clinical application. With an improved gentleand fast isolation process by minor manipulation it is possible to obtain a therapeuticallyrelevant cell population. A physical stimulus already used in clinics is the extracorporealshockwave therapy (ESWT), shockwaves are characterized by their high rise in pressurewithin a very short time followed by cavitation wave with a negative amplitude. By applyinglow-energy ESWT on freshly obtained human liposuction material and isolated SVF cells (invitro) we aimed to equalize and enhance stem cell properties and their functionality. We wereable to show an increased adenosine tri-phosphate (ATP) concentration after applying ESWTon adipose tissue as well as a significantly increased expression of single mesenchymal andvascular surface markers in comparison with the untreated group. Additionally, the proteinsecretion of insulin-like growth factor 1 (IGF-1) and placental growth factor (PLGF) wassignificantly enhanced. Further it was investigated if there is the same beneficial effect whenapplying ESWT on the adipose tissue harvest site before liposuction to improve cell propertiesin situ. We showed a significantly enhanced viability, ATP concentration and populationdoublings after 3 weeks in culture for cells isolated from ESW treated adipose tissue harvestsite. Further the expression of mesenchymal and endothelial/pericytic markers was elevatedcollaborating with the increased angiogenic differentiation potential as well as the increasedsecretion of certain angiogenic proteins after ESWT in situ. Besides ESWT the effect of anotherphysical stimulus on SVF/ASC cells was tested - Low level laser therapy (LLLT) has alreadyshown beneficial effects. Therefore, we investigated effects of pulsed blue (475nm), green(516nm) and red (635nm) light from light-emitting diodes (LEDs) applied on freshly isolatedSVF cells. Cells had a stronger capacity to vascular tube formation after exposure to greenand red light concomitant with an increased concentration of vascular endothelial growth factor(VEGF) in the secretome. In a side project during the PhD program the hormone-relatedwomens disease lipedema was investigated. The SVF cell properties of healthy and lipedemapatients were investigated and a significant enhancement in cell yield as well as a reduction inadipogenic differentiation capacity of lipedema SVF cells was revealed. Within this workdifferent physical forces applied on adipose tissue and adipose tissue-derived cells werepresented as well as an improved isolation method and characteristics of degenerated adiposetissue. This are promising applications for the clinical use in the field of regenerative medicineand tissue regeneration.

The objective of the present study was to report that aggravating factors of lymphatic or venous edema contribute to aggravate the evolution of lymphedema. A 54-year-old women with a six-year history of venous thrombosis of the left leg reported that her family had thicker arms and legs and that she had inherited this genetic trait. Electrical bioimpedance analysis was performed with the In Body S10 device. The exam revealed total intracellular and extracellular water beyond the parameters of normality as well as water in the thorax and limbs. In the lower limbs, the total extracellular water/total body water ratio also surpassed the limits of normality. The findings demonstrated bilateral lower limb lymphedema with clinical signs in the left leg. Obesity can trigger a new concept of lymphedema that we denominate subclinical systemic lymphedema, which is characterized by an increase in body water. Moreover, aggravating processes of the venous system, such as deep vein thrombosis, can aggravate the edema.

Aim: The aim of the present study was to evaluate the prevalence of subclinical and clinical systemic lymphedema in patients with lipedema and different body mass index (BMI) values., Method: A cross-sectional study was conducted to determine the prevalence of subclinical systemic lymphedema and clinical lymphedema of the lower limbs detected by bioimpedance (InBody S10 device, Seoul, Korea) in 258 women with clinically diagnosed lipedema. The patients were divided into three groups based on BMI: Group I - BMI below 30 kg/m2; Group II - BMI between 30 and 40 kg/m2; and Group III - BMI 40 to 50 kg/m2., Results: Fisher's exact test revealed a statistically significant difference between Group I and both Groups II and III (p = 0.0001) regarding the occurrence of lower limb lymphedema., Conclusion: Patients with lipedema can develop edema even when their weight is within the standards of normality. However, obesity is an aggravating factor, as the prevalence of lipedema increases progressively with the increase in weight.

Summary Lipedema is a painful, chronically progressive disease that is characterized by a symmetrical increase in subcutaneous fat with fluid accumulation on the legs and / or arms. Due to ignorance of the clinical picture, the disease is often not recognized or misinterpreted. Correct diagnosis and treatment are important, however, as the prognosis of the disease can be influenced. A causal therapy for lipedema is not known because the exact etiology is not yet fully understood. A hereditary component is suspected on the basis of a family history of the disease. Since lipedema occurs almost exclusively in women and the onset of the disease is often associated with the onset of hormonal changes (puberty, pregnancy, menopause), In addition, the estrogen is assigned a decisive role in the development. In the present work we present an overview of the symptoms and clinical features of lipedema, its differential diagnoses, treatment options and, lastly, the current hypotheses on the pathogenesis of lipedema.

IN JUNE 2020, the Lipedema ICD-10-CM Committee, with support from the American Vein & Lymphatic Society (AVLS), submitted an application to the US Centers for Disease Control and Prevention to establish new ICD-10-CM codes for lipedema and lipolymphedema, two related adipose tissue disorders. Currently,

Patients with obesity-associated lipoedema minimize by diet only the regular fat especially in the lower leg area. The pathological lipoedema with a possible secondary lymphodynamic oedema remains and causes skin irritation, discomfort and pain wearing the compression elements. The dorsal lower leg lift with previous liposuction is a useful therapeutic strategy to overcome these difficulties. A 37-year-old female patient after post-bariatric surgery and massive weight loss (MWL) presented with a lower leg lipoedema and lymphodynamic oedema. She underwent a liposuction removing lipoedema of the lower leg followed by a calf lift procedure on both sides. With sufficient surgical experience in skin tightening surgery after MWL, a significant improvement in day-to-day problems in patients with lipoedema can be achieved by dorsal lift of the lower leg after liposuction.

Background: Lipedema and Dercum's disease (DD) are incompletely characterized adipose tissue diseases, and objective measures of disease profiles are needed to aid in differential diagnosis. We hypothesized that fluid properties, quantified as tissue water bioimpedance in the upper and lower extremities, differ regionally between these conditions. Methods and Results: Women (cumulative n = 156) with lipedema (n = 110), DD (n = 25), or without an adipose disease matched for age and body mass index to early stage lipedema patients (i.e., controls n = 21) were enrolled. Bioimpedance spectroscopy (BIS) was applied to measure impedance values in the arms and legs, indicative of extracellular water levels. Impedance values were recorded for each limb, as well as the leg-to-arm impedance ratio. Regression models were applied to evaluate hypothesized relationships between impedance and clinical indicators of disease (significance criteria: two-sided p < 0.05). Higher extracellular water was indicated (i) in the legs of patients with higher compared with lower stages of lipedema (p = 0.03), (ii) in the leg-to-arm impedance ratio in patients with lipedema compared with patients with DD (p ≤ 0.001), and (iii) in the leg-to-arm impedance ratio in patients with stage 1 lipedema compared with controls (p ≤ 0.01). Conclusion: BIS is a noninvasive portable modality to assess tissue water, and this device is available in both specialized and nonspecialized centers. These findings support that regional bioimpedance measures may help to distinguish lipedema from DD, as well as to identify early stages of lipedema.

Background: Lipedema and Dercum's disease (DD) are incompletely characterized adipose tissue diseases, and objective measures of disease profiles are needed to aid in differential diagnosis. We hypothesized that fluid properties, quantified as tissue water bioimpedance in the upper and lower extremities, differ regionally between these conditions. Methods and Results: Women (cumulative n = 156) with lipedema (n = 110), DD (n = 25), or without an adipose disease matched for age and body mass index to early stage lipedema patients (i.e., controls n = 21) were enrolled. Bioimpedance spectroscopy (BIS) was applied to measure impedance values in the arms and legs, indicative of extracellular water levels. Impedance values were recorded for each limb, as well as the leg-to-arm impedance ratio. Regression models were applied to evaluate hypothesized relationships between impedance and clinical indicators of disease (significance criteria: two-sided p < 0.05). Higher extracellular water was indicated (i) in the legs of patients with higher compared with lower stages of lipedema (p = 0.03), (ii) in the leg-to-arm impedance ratio in patients with lipedema compared with patients with DD (p ≤ 0.001), and (iii) in the leg-to-arm impedance ratio in patients with stage 1 lipedema compared with controls (p ≤ 0.01). Conclusion: BIS is a noninvasive portable modality to assess tissue water, and this device is available in both specialized and nonspecialized centers. These findings support that regional bioimpedance measures may help to distinguish lipedema from DD, as well as to identify early stages of lipedema.