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In contrast to obesity, which is very frequent, lipomatosis and lipodystrophy syndromes are rare diseases of adipose tissue. Lipodystrophy syndromes are characterized by metabolic abnormalities associated with partial or generalized lipoatrophy. Lipomatosis is defined by the presence of several body lipomas without lipoatrophy. Dercum’s disease (DD) and Roch-Leri mesosomatous lipomatosis (RLML) are rare and poorly characterized forms of lipomatosis. They have raised little clinical interest despite the non-negligible consequences of DD on quality of life. The main clinical presentation of these diseases includes multiple lipomas, which are painful in DD (in contrast to RLML). The two diseases are frequently associated with obesity and metabolic syndrome, with hypertension, diabetes, or dyslipidemia. The long-term course of the diseases remains poorly described. DD affects mainly women, whereas RLML mostly affects men. In both diseases lipomas are found on the back and thighs, as well as on the abdomen in DD and the forearms in RLML. The painful lipomas tend to recur after surgery in DD (in contrast to RLML). Most cases are sporadic. No specific treatment has been identified, as the pathophysiology remains unknown. Nevertheless, low-grade fat inflammation and specific abnormalities such as hyperbasophilia deserve further investigation. The aim of this review is to analyze the available literature on the topic.

The adipose tissue stroma is a rich source of molecularly distinct stem and progenitor cell populations with diverse functions in metabolic regulation, adipogenesis, and inflammation. The ontology of these populations and the mechanisms that govern their behaviors in response to stimuli, such as overfeeding, however, are unclear. Here, we show that the developmental fates and functional properties of adipose platelet-derived growth factor receptor beta (PDGFRβ)+ progenitor subpopulations are tightly regulated by mitochondrial metabolism. Reducing the mitochondrial β-oxidative capacity of PDGFRβ+ cells via inducible expression of MitoNEET drives a pro-inflammatory phenotype in adipose progenitors and alters lineage commitment. Furthermore, disrupting mitochondrial function in PDGFRβ+ cells rapidly induces alterations in immune cell composition in lean mice and impacts expansion of adipose tissue in diet-induced obesity. The adverse effects on adipose tissue remodeling can be reversed by restoring mitochondrial activity in progenitors, suggesting therapeutic potential for targeting energy metabolism in these cells.

Lipoedema is a subcutaneous adipose tissue disease characterized by the increase in the amount and structure of fat mass (FM) in specific areas, causing pain and discomfort. 95% of patients fail to lose weight in the lipoedema areas. The study was conducted to evaluate body composition and general health status modification in a group of lipoedema patients (LIPPY) and a control group (CTRL) after four weeks of a modified Mediterranean diet therapy (mMeD). A total of 29 subjects were included in the data analysis, divided in two groups: 14 LIPPY and 15 CTRL. After the mMeD, both groups significantly decreased their weight and body mass index; the CTRL also showed a reduction of all the circumferences and all FM's compartments. LIPPY showed a decrease of FM in upper and lower limbs. No significant differences in Δ% between the groups were observed for the lean mass (LM). In LIPPY, an increase in the patients' ability to perform various daily physical activities related to the loss of arms' and legs' fat was observed. According to the European Quality of Life scale, the possibility for LIPPY subjects to perform simple daily activities with less fatigue, pain and anxiety is highlighted. Further long-term studies are recommended to confirm the mMeD as a good strategy for Lipoedema treatment.

Lipedema is a type of subcutaneous adipose tissue disorder that affects mainly women. Its main symptom is bilateral fat accumulation on the extremities with associated pain in the affected areas. Despite growing interest in lipedema among patients and medical health professionals, lipedema is still often misdiagnosed, misunderstood, and mistreated. To promote better understanding of lipedema, we aimed to investigate factors related to the quality of life and describe selected sociodemographic and clinical characteristics of women with lipedema in Poland.

Primary lymphedema is a rare chronic pathology associated with constitutional abnormalities of the lymphatic system. The objective of this French National Diagnosis and Care Protocol (Protocole National de Diagnostic et de Soins; PNDS), based on a critical literature review and multidisciplinary expert consensus, is to provide health professionals with an explanation of the optimal management and care of patients with primary lymphedema. This PNDS, written by consultants at the French National Referral Center for Primary Lymphedema, was published in 2019 (https://has-sante.fr/upload/docs/application/pdf/2019-02/pnds_lymphoedeme_primaire_final_has.pdf). Primary lymphedema can be isolated or syndromic (whose manifestations are more complex with a group of symptoms) and mainly affects the lower limbs, or, much more rarely, upper limbs or external genitalia. Women are more frequently affected than men, preferentially young. The diagnosis is clinical, associating mild or non-pitting edema and skin thickening, as confirmed by the Stemmer’s sign (impossibility to pinch the skin on the dorsal side or the base of the second toe), which is pathognomonic of lymphedema. Limb lymphoscintigraphy is useful to confirm the diagnosis. Other causes of swelling or edema of the lower limbs must be ruled out, such as lipedema. The main acute lymphedema complication is cellulitis (erysipelas). Functional and psychological repercussions can be major, deteriorating the patient’s quality of life. Treatment aims to prevent those complications, reduce the volume with low-stretch bandages, then stabilize it over the long term by exercises and wearing a compression garment. Patient education (or parents of a child) is essential to improve observance.

Lipedema is a painful, underdiagnosed adipose tissue disorder, characterized by symmetrical swelling of the extremities due to subcutaneous fat deposition in the buttocks, thighs, legs, and arms, sparing the most distal part of the extremities. Although etiology and pathogenesis of lipedema is unclear, possible role of hormonal and genetic factors have been proposed previously. Patients with lipedema suffer from pain, easy bruising, tenderness, and disfigurement. Pain is the leading symptom in lipedema. Since the pain is associated with depression and impaired quality of life, reduction of pain is the major therapeutic approach. Pain in lipedema is attributed to allodynia, exaggerated sympathetic signaling, and estrogens. Although the mechanism of pain in lipedema is uncertain, effective treatment of lipedema should provide a satisfactory pain reduction. Efficacy of the conservative treatment is a matter of debate. Microcannular tumescent liposuction is the most effective therapeutic option for lipedema. There is a large body of evidence that this procedure significantly reduces pain in patients with lipedema.

Lipedema is an adipose tissue disorder characterized by the disproportionate increase of subcutaneous fat tissue in the lower and/or upper extremities. The underlying pathomechanism remains unclear and no molecular biomarkers to distinguish the disease exist, leading to a large number of undiagnosed and misdiagnosed patients. To unravel the distinct molecular characteristic of lipedema we performed lipidomic analysis of the adipose tissue and serum of lipedema versus anatomically- and body mass index (BMI)-matched control patients. Both tissue groups showed no significant changes regarding lipid composition. As hyperplastic adipose tissue represents low-grade inflammation, the potential systemic effects on circulating cytokines were evaluated in lipedema and control patients using the Multiplex immunoassay system. Interestingly, increased systemic levels of interleukin 11 (p = 0.03), interleukin 28A (p = 0.04) and interleukin 29 (p = 0.04) were observed. As cytokines can influence metabolic activity, the metabolic phenotype of the stromal vascular fraction was examined, revealing significantly increased mitochondrial respiration in lipedema. In conclusion, despite sharing a comparable lipid profile with healthy adipose tissue, lipedema is characterized by a distinct systemic cytokine profile and metabolic activity of the stromal vascular fraction.

Over the last decade, stem cell-based regenerative medicine has progressed to clinical testing and therapeutic applications. The applications range from infusions of autologous and allogeneic stem cells to stem cell-derived products. Adult stem cells from adipose tissue (ASCs) show significant promise in treating autoimmune and neurodegenerative diseases, vascular and metabolic diseases, bone and cartilage regeneration and wound defects. The regenerative capabilities of ASCs in vivo are primarily orchestrated by their secretome of paracrine factors and cell-matrix interactions. More recent developments are focused on creating more complex structures such as 3D organoids, tissue elements and eventually fully functional tissues and organs to replace or repair diseased or damaged tissues. The current and future applications for ASCs in regenerative medicine are discussed here.

Objective: To examine the common and specific characteristics of fibromyalgia and lipe­ dema, two chronic soft-tissue pain syndromes without curative therapy options. Methods: Diseases’ characteristics were compared using the findings of extensive literature and the empiric data from two cohorts, both fulfilling standardized diagnostic criteria. Outcome was measured by various socio-demographics, the generic Short Form 36 (SF36), the Fibromyalgia Severity Questionnaire (FSQ), and the 6-minute walk distance (6MWD). Empiric SF-36 data were compared to specific population-based norms and between the diagnostic groups, using standardized mean differences (SMD). Results: Female participants with fibromyalgia (n = 77) and lipedema (n = 112) showed comparable education levels and living situations. Lipedema cases were, on average, 3.9 years younger and BMI 6.3kg/m2 more obese. Women with fibromyalgia smoked more, did less sport, had more comorbidities, and worked less. Compared to the norms, health in fibromyalgia was worse than expected by SMD = –1.60 to –2.35 and in lipedema by –0.44 to –0.82 on the SF-36. The score differences between the two conditions ranged from SMD = –0.96 to –1.34 (all p < 0.001) on the SF-36 and the FSQ. For the inpatients (n = 77 fibromyalgia, n = 38 lipedema), the 6MWD was comparable (SMD = –0.09, p = 0.640). These findings were consistent with detailed data from the literature reviewed. Discussion: Fibromyalgia and lipedema share characteristics of clinical phenomenology and comorbid conditions. Disease perception is more pronounced in fibromyalgia than in lipe­dema, especially in social and role dysfunction, whereas the walking distance was similar for both syndromes. This difference may be explicable by limited coping skills in fibromyalgia.

Currently, the ketogenic diet (KD) is used to treat obesity. A prospective study on the use of KD and nutraceutical correction of the nutritional status of patients with lipedema was carried out. Aim. To study the effect of the ketogenic diet, accompanied by correction of changes in the intestinal microbiome and hepatoprotection,on the reduction of fatty deposits in lipedema and the dynamics of changes in lipid and carbohydrate metabolism hormones. Material and methods. 60 patients with lower limb lipedema of stages I-III were randomized into 2 groups: Group 1 received a lowcalorie diet (LCD), physical exercises in the gym (PE), and physical activity (FA) in the form of daily walking up to 3-5 km/ day. Group 2 received a modified version of the Atkins ketogenic diet, physical exercises in the gym and FA, as well as nutraceutical correction of increased appetite, probiotic intestinal composition, hepatoprotection. The duration of the treatment course was 4 weeks. Anthropometric methods and bioimpedansometry were used to control limb circumferences, waist and thigh. Results and discussion. After treatment, patients in 1st group showed a decrease in body weight, lean and active cell mass, a decrease in musculoskeletal mass, and a decrease in total water due to extracellular water. A decrease in total cholesterol and high density lipoproteins (HDL) fraction, an increase in blood triglyceride fraction was noted. Leptin decreased by 12.73%. Patients of the 2nd group showed a decrease in body weight, fat mass, lean mass, total water and extracellular water. There was a decrease in total cholesterol, triglycerides, transaminases. Leptin decreased by 32.02%, insulin decreased by 9.87%. To prevent the development of fatty hepatosis against the background of the use of KD, patients of the 2nd group received nutraceutical correction: hepatoprotector Gepamin, metaprebiotic Stimbifid-plus, modulating the formation of resident intestinal microbiota. To reduce appetite, the patients of the 2nd group were also prescribed anorexic - an algal product Nativ containing the polysaccharide fucoidan, having a prebiotic effect. Improvement of reparative processes in the liver, suppression of oxidative processes also contributed to the restoration of the sensitivity of insulin receptors, which was confirmed by the normalization of the lipid-carbohydrate spectrum of blood in patients of the 2nd group after the course of the treatment. The insulin decrease in patients of Group 2 indicated not only insulin resistance decrease , but also the lipogenesis decrease and stimulation of lipolysis. Adipose tissue reduction due to lipolysis stimulation was also indicated by a decrease in leptin expression. Conclusion. Thus, a ketogenic diet, accompanied by nutraceutical correction of the intestinal microbiome and hepatoprotection can be effectively used in combination with physical activity in order to reduce body weight, fat mass and edema, as evidenced by a decrease in the expression level of leptin and insulin, correlating with the levels of fat loss and free water.

Lipedema is a chronic disease seen frequently in women that causes abnormal fat deposition in the lower limbs and associated bruising and pain. Despite increasing knowledge concerning lipedema, there are still aspects of diagnosis that need further investigation. We performed a prospective, observational cohort study to describe prevalence of clinical characteristics present in patients with lipedema in an attempt to establish diagnostic criteria. Participants were consecutive patients with lipedema presenting at a public hospital in Spain from September 2012 to December 2019. Patients were examined for the following signs and symptoms of lipedema: symmetrical involvement; disproportion between the upper and lower part of the body; sparing of the feet; pain; bruising; Stemmer' sign; pitting test; fibrosis; venous insufficiency; upper limbs involvement; vascular spiders; skin coldness; and lymphangitis attacks. In addition, orthopedic alterations were examined in all patients. We recruited 138 patients (median age=47.6 years; mean BMI=29.9 Kg/m2). Using waist-to-height-ratio, 41.3% of the patients were slim or healthy. The most frequent type of lipedema was Type III (71%), and most were in stage 1 and 2. The features of lipedema with a prevalence >80% were symmetrical involvement, unaffected feet, pain, bruising, vascular spiders, and disproportion. Pain was nociceptive in 60.2% and neuropathic in 33.1%, and there was a reduced social or working activities in 37.9%. Orthopedic alterations including cavusfeet or valgus-knees were observed in 1/3 of the patients. X-ray of the knees was performed in 63 patients and knee osteoarthritis diagnosed in 37. We found that the most frequent manifestations of lipedema were bilateral involvement, unaffected feet, pain, easy bruising, vascular spiders, and disproportion between the upper and lower parts of the body. These should be considered as major criteria for diagnosis. In addition, our findings on the prevalence of orthopedic alterations in patients with lipedema highlights the need for a multidisciplinary and integrated approach.

Background: Lipedema is a chronic disorder of the adipose tissue that affects mainly women, characterised by symmetrical, excessive fatty tissue on the legs and pain. Standard conservative treatment is long-term comprehensive decongestive therapy (CDT) to alleviate lipedema-related pain and to improve psychosocial wellbeing, mobility and physical activity. Patients may benefit from surgical removal of abnormally propagated adipose tissue by liposuction. The LIPLEG trial evaluates the efficacy and safety of liposuction compared to standard CDT. Methods/design: LIPLEG is a randomised controlled multicentre investigator-blinded trial. Women with lipedema (n=405) without previous liposuction will be allocated 2:1 to liposuction or CDT. The primary outcome of the trial is leg pain reduction by ≥2 points on a visual analogue scale ranging 0–10 at 12 months on CDT or post-completion of liposuction. Secondary outcomes include changes in leg pain severity, health-related quality of life, depression tendency, haematoma tendency, prevalence of oedema, modification physical therapy scope, body fat percentage, leg circumference and movement restriction. The primary analysis bases on intention-to-treat. Success proportions are compared using the Mantel-Haenszel test stratified by lipedema stage at a 5% two-sided significance level. If this test is statistically significant, the equality of the response proportions in the separate strata is evaluated by Fisher’s exact test in a hierarchical test strategy. Discussion: LIPLEG assesses whether surgical treatment of lipedema is safe and effective to reduce pain and other lipedema-related health issues. The findings of this trial have the potential to change the standard of care in lipedema. Trial registration: ClinicalTrials.gov NCT04272827. Registered on February 14, 2020. Trial status: Protocol version is 02_0, December 17, 2019

Iliac vein compression (IVC) is a common anatomic disorder affecting more than 20% of the adult population, especially young females. Most of those patients are asymptomatic. Some of them will develop symptoms in their left leg, such as swelling, pain, and heaviness. But progression to venous claudication, skin changes, and even venous ulceration is possible. Intolerance to exercise is an undervalued symptom. The most feared complication is the development of a deep venous thrombosis (DVT) and pulmonary embolism (PE). In addition to the symptomatology, the diagnosis can be confirmed using duplex ultrasound, computed tomographic (CT) scan, or magnetic resonance (MR) venography. However, for the exact measurement of the degree of stenosis and indication for stenting, intravascular ultrasound (IVUS) is the preferred tool for assessing iliac vein compression. Those patients are, especially in combination with other risk factors, at higher risk for developing DVT and PE. However, it is difficult to identify the patients who will benefit from a treatment (stenting) in terms of symptomatology and quality of life (QOL) or even in effective DVT prevention. Venous stenting is the treatment of choice and seems to be safe and effective. Poststenting antiplatelet medication is most appropriate for patients with nonthrombotic IVC, whereas postthrombotic patients should preferably be treated with oral anticoagulants. Meticulous selection of patients for treatment is necessary to avoid over-treatment.

The term lipedema is misleading, although it is true that there is an alteration of the fatty tissue, there is little evidence regarding edema. It is considered a disease since the last ICD‑11 (2019), included in the section of pathologies of skin, fat and subcutaneous cellular tissue. However, there are still doubts about whether it should be considered a disease or whether it is an aesthetic disorder. The diagnosis of lipedema can present challenges, since it is often confused with other nosological entities; especially with lymphedema. The aim of this task is to determine the basis for a correct differential diagnosis that helps to recognize lipedema as an entity with its own characteristics in order to facilitate its early identification. Clinical manifestations, plus the anamnesis and detailed examination of each patient, may be sufficient to reach a correct diagnosis. In case of doubt, there are tests capable of differentiating between lipedema and lymphedema. Differential diagnosis between lipedema and lymphedema should be made thoroughly and early in order to offer early advice and specific treatment to patients.

Lipedema is a chronic and progressive disease characterized by a symmetrical and bilateral swelling of the lower extremities. In general, the feet are not involved. Lipedema is believed to affect nearly 1 in 9 adult women worldwide. Despite this relatively common disease, lipedema is often confused with primary lymphedema or obesity. In clinically advanced lipedema stages, fat continues to build up and may block the lymphatic vessels causing a secondary lymphedema (Lipo-Lymphedema). We consecutively evaluated 54 women with a clinical diagnosis of lower limbs lipedema. Two doses of 99mTc-nanocolloid were injected intradermally at the first intermetatarsal space and in the lateral malleolar area. Two static planar scans were taken at rest immediately following the intradermal injection. Subsequently, all patients were asked to perform an isotonic muscular exercise (stepping) for 2 min. Then, post exercise scans were performed to monitor the tracer pathway. Subsequently, the patient was asked to take a 30-40 min walk (prolonged exercise) and delayed scans were acquired. In early clinical stages, the lymphatic flow is usually preserved and the rest/stress intradermal lymphoscintigraphy may visualize a normal lymphatic drainage with a frequent pattern (tortuous course) of the leg lymphatic pathway. In clinically advanced stages, lymph stagnation areas were observed. Unlike obesity, lipedema fat storage is resistant to dietary regimen, bariatric surgery, and physical activity. Surgical treatment (tumescent liposuction and reductive surgery) is the most effective treatment to remove adipose tissue. Complex decongestive therapies are helpful in reducing the lymph stagnation, especially in patients with advanced lipolymphedema.

Lipedema (LI) is a common yet misdiagnosed condition, often misconstrued with obesity. LI affects women almost exclusively, and its painful and life-changing symptoms have long been thought to be resistant to the lifestyle interventions such as diet and exercise. In this paper, we discuss possible mechanisms by which patients adopting a ketogenic diet (KD) can alleviate many of the unwanted clinical features of LI. This paper is also an effort to provide evidence for the hypothesis of the potency of this dietary intervention for addressing the symptoms of LI. Specifically, we examine the scientific evidence of effectiveness of adopting a KD by patients to alleviate clinical features associated with LI, including excessive and disproportionate lower body adipose tissue (AT) deposition, pain, and reduction in quality of life (QoL). We also explore several clinical features of LI currently under debate, including the potential existence and nature of edema, metabolic and hormonal dysfunction, inflammation, and fibrosis. The effectiveness of a KD on addressing clinical features of LI has been demonstrated in human studies, and shows promise as an intervention for LI. We hope this paper leads to an improved understanding of optimal nutritional management for patients with LI and stimulates future research in this area of study.