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Representation of subcutaneous adipose tissue (SAT) characteristics pattern in lipedema. (A) The SAT location and deposition in the body; (B) skin tissue cube presenting their residing components; (C) characteristics of lean adipose tissue accompanied by ECM, immune cells, and various forms of typical fat droplets; (D) hypertrophy and hyperplasia in SAT with immune-cell requirements; and (E) inflammation, excessive fluid deposition, and swelling in the upper leg/thigh, which are the common characteristic of individuals with lipedema.
Source publication
Lipedema is an adipofascial disorder that almost exclusively affects women. Lipedema leads to chronic pain, swelling, and other discomforts due to the bilateral and asymmetrical expansion of subcutaneous adipose tissue. Although various distinctive morphological characteristics, such as the hyperproliferation of fat cells, fibrosis, and inflammatio...
Citations
... this progression are not yet clear. Numerous studies were conducted to explore potential molecular alterations distinguishing lipedema from non-lipedema adipose tissue in vivo and in vitro (reviewed in [21,22]). Thereby, a major focus was set on the appearance of hyperplasia and hypertrophy, two basic mechanisms underlying adipose tissue accumulation [27,28], and on the role of low-level inflammation and fibrotic changes in the development of lipedema [29]. ...
... In the present study, we have followed gene expression and in vitro growth of ASCs and fully differentiated adipocytes derived from the SVF of lipoaspirates from lipedema and control donors. Since we and others have shown previously that lipedema adipocytes differ from non-lipedema adipocytes by increased expression of adipogenesis-related genes (reviewed in [21,22]), we went on to identify additional characteristics distinguishing lipedema adipocytes from their healthy counterparts. ...
Despite extensive research during the last couple of years, lipedema still appears enigmatic in respect to its pathogenesis. In our in vitro study, we have set out to further characterize lipedema adipocytes, concentrating on gene and protein expression, which might help to develop ideas explaining the excessive accumulation of adipose tissue in women with lipedema. Using 2D cultures we show that gene expression in lipedema and non-lipedema adipocytes differs significantly in terms of genes related to lipid droplet size determination, insulin signaling and glucose uptake. A pronounced hypertrophy, recognizable by a significantly increased average lipid droplet size, was visible in differentiated lipedema adipocytes grown in 3D cultures. In addition, gene and protein expression related to inflammation and fibrosis were upregulated in lipedema adipocytes compared to controls, supporting earlier reports. Taken together, results from our in vitro studies suggest that lipedema adipose cells are capable of retaining their hypertrophic nature under culture conditions and open new aspects focusing on insulin signaling and PDGFRA-mediated balancing of adipogenic versus fibrogenic differentiation of lipedema adipose tissue.
... Since most lipedema patients have elevated BMI due to pathologically engorged adipocyte, this cohort often shows vitamin D deficiency as well. These patients not only display low vitamin D serum levels due to its inverse correlation to BMI but also because engorged and inflamed adipocytes in lipedema traps vitamin D [14,[40][41][42]. This bidirectional relationship between vitamin D deficiency and elevated BMI with low serum vitamin D levels is also evident in our study. ...
... Since liposuction is the gold standard in treating lipedema, patients already suffering from vitamin D deficiency are at risk of further vitamin D loss. The lack of vitamin D has already been linked to entailing chronic cellular stress, which can be seen in lipedema patients [40,42,45]. By further diminishing vitamin D levels after liposuction, patients experiencing lipedema further maintain oxidative stress, resulting in sustained lipedema symptoms [14,42,45]. ...
Background: Lipedema is a subcutaneous adipose tissue disorder characterized by increased pathological adipocytes mainly in the extremities. Vitamin D is stored in adipocytes, and serum levels inversely correlate with BMI. As adipocytes are removed during liposuction, lipedema patients might be prone to further substantial vitamin D loss while their levels are already decreased. Therefore, we examined the effect of liposuction on perioperative serum 25-hydroxyvitamin D levels. Methods: In patients undergoing lipedema liposuction, blood samples were obtained pre- and postoperatively. Statistical analyses were performed to correlate the volume of lipoaspirate, patients’ BMI and number of sessions to vitamin D levels. Results: Overall, 213 patients were analyzed. Mean liposuction volume was 6615.33 ± 3884.25 mL, mean BMI was 32.18 ± 7.26 kg/m². mean preoperative vitamin D levels were 30.1 ± 14.45 ng/mL (borderline deficient according to the endocrine society) and mean postoperative vitamin D levels were 21.91 ± 9.18 ng/mL (deficient). A significant decrease in serum vitamin D was seen in our patients (p < 0.001) of mean 7.83 ng/mL. The amount of vitamin D loss was not associated with BMI or aspiration volume in our patients (p > 0.05). Interestingly, vitamin D dynamics showed a steady drop regardless of volume aspirated or preoperative levels. Conclusions: Many lipedema patients have low vitamin D levels preoperatively. Liposuction significantly reduced these levels additionally, regardless of aspirated volume or BMI. However, vitamin D loss was constant and predictable; thus, patients at risk are easily identified. Overall, lipedema patients undergoing liposuction are prone to vitamin D deficiency, and the long-term effects in this population are currently unknown.
... The bodily appearance of lipedema is often confused with obesity and lymphedema. Women with lipedema experience tenderness, heaviness of affected limbs, and difficulty in losing weight as the fat tissue is highly resistant to diet and exercise [4,5]. Lipedema patients can be categorized into four stages based on the severity of adipose tissue accumulation in the extremities. ...
Lipedema is a chronic, idiopathic, and painful disease characterized by an excess of adipose tissue in the extremities. The goal of this study is to characterize the gene expression of estrogen receptors (ERα and ERβ), G protein-coupled estrogen receptor (GPER), and ER-metabolizing enzymes: hydroxysteroid 17-beta dehydrogenase (HSD17B1, 7, B12), cytochrome P450 (CYP19A1), hormone-sensitive lipase (LIPE), enzyme steroid sulfatase (STS), and estrogen sulfotransferase (SULT1E1), which are markers in Body Mass Index (BMI) and age-matched non-lipedema (healthy) and lipedema ASCs and spheroids. Flow cytometry and cellular proliferation assays, RT-PCR, and Western Blot techniques were used to determine the expression of ERs and estrogen-metabolizing enzymes. In 2D monolayer culture, estrogen increased the proliferation and the expression of the mesenchymal marker, CD73, in hormone-depleted (HD) healthy ASCs compared to lipedema ASCs. The expression of ERβ was significantly increased in HD lipedema ASCs and spheroids compared to corresponding healthy cells. In contrast, ERα and GPER gene expression was significantly decreased in estrogen-treated lipedema spheroids. CYP19A1 and LIPE gene expressions were significantly increased in estrogen-treated healthy ASCs and spheroids, respectively, while estrogen upregulated the expression of PPAR-ϒ2 and ERα in estrogen-treated lipedema-differentiated adipocytes and spheroids. These results indicate that estrogen may play a role in adipose tissue dysregulation in lipedema.
... Nicméně v pokročilém stadiu lipedému může docházet podobně jako u jiných hyperosmolárních otoků k postupné fibróze podkožní tkáně. Nadměrná akumulace tekutiny v intersticiálním prostoru často představuje znak progresivního lipedému (7). Neléčený lipedém v přítomnosti obezity může vést k sekundárnímu lymfedému (1). ...
Lipedema, a chronic disease characterized by excessive fatty tissue deposition in the hips, buttocks, and lower legs, significantly negatively impacts the quality of life of those affected. This disease, which almost exclusively affects women, is often underdiagnosed, and confused with obesity. Diagnosis of lipedema is crucial for initial treatment and improvement of the patient's quality of life. Hormonal changes, inflammation, and tissue fibrosis play an essential role in the pathogenesis of lipedema.
This article presents nutritional strategies that may bring relief to patients with lipedema. Nutritional intervention for lipedema patients could be an adjunct to traditional treatment, improving quality of life and reducing pain. However, these findings must be subjected to further research and clinical trials. The exact mechanism by which diet affects lipedema remains incompletely understood and, therefore, requires further study. However, this work provides hope and direction for future therapeutic approaches and research in treating lipedema.
... However, it is interesting to note that lipedema can coexist with a state of obesity, which in turn can promote a state of chronic low-grade inflammation [13]. This state of chronic low-grade inflammation in turn can impair lymphatic function, exacerbating adipose tissue accumulation [13]. ...
... However, it is interesting to note that lipedema can coexist with a state of obesity, which in turn can promote a state of chronic low-grade inflammation [13]. This state of chronic low-grade inflammation in turn can impair lymphatic function, exacerbating adipose tissue accumulation [13]. Thus, lipedema, obesity, and inflammation form an unfavorable vicious cycle. ...
... The lymphatic vasculature in lipedema shows increased permeability with a larger interstitial space [83]. Several novel potential biomarkers for lipedema in the last few years have been described [13]. Platelet factor 4 has shown promising results as a biomarker for lymphatic diseases, both in animal models and human studies [84]. ...
Purpose of Review
This review aims to provide an overview of the current evidence on the efficacy, also considering the anti-inflammatory properties and safety of very low-calorie ketogenic diet (VLCKD) as a potential treatment for lipedema, particularly in the context of obesity.
Recent Findings
Lipedema is a chronic disease characterized by abnormal and painful fat buildup on the legs and/or arms. It is often misdiagnosed as obesity or lymphedema. However, although lipedema and obesity can coexist, unlike obesity, lipedema usually affects the legs and thighs without affecting the feet or hands, and the abnormal deposition of adipose tissue in lipedema is painful. The current lifestyle interventions are often unsuccessful in the management of lipedema. There is no consensus on the most effective nutritional approach for managing lipedema. Recent studies have suggested that VLCKD may be an effective treatment for lipedema, demonstrating that it is also superior to other nutritional approaches such as Mediterranean diet or intermittent fasting.
Summary
Lipedema is a chronic and debilitating disease characterized by abnormal and painful accumulation of adipose tissue in the legs. VLCKD has been shown to be an effective treatment for lipedema, especially in the context of obesity, due to its anti-inflammatory properties. However, further research is needed to determine the long-term safety and efficacy of VLCKD as a treatment for lipedema.
... One prominent downstream mediator of the MIF-1-CD74 interaction is the downstream monocyte chemoattractant protein 1 (MCP-1) upregulation, e.g., through the p38 MAPK [50]. MCP-1 in return is a key chemokine secreted by macrophages that induces ASC proliferation and at the same time inhibits adipogenesis, which may play a role in lipedema [51]. Other downstream molecules or pathways that may play a role in lipedema include p-NF-κB and p-STAT3 as both have known correlations with obesity and adipose inflammation. ...
Lipedema is a chronic disorder that mainly affects women. It is often misdiagnosed, and its etiology remains unknown. Recent research indicates an accumulation of macrophages and a shift in macrophage polarization in lipedema. One known protein superfamily that contributes to macrophage accumulation and polarization is the macrophage migration inhibitory factor (MIF) family. MIF-1 and MIF-2 are ubiquitously expressed and also regulate inflammatory processes in adipose tissue. In this study, the expression of MIF-1, MIF-2 and CD74—a common receptor for both cytokines—was analyzed in tissue samples of 11 lipedema and 11 BMI-matched, age-matched and anatomically matched control patients using qPCR and immunohistochemistry (IHC). The mRNA expression of MIF-1 (mean 1.256; SD 0.303; p = 0.0485) and CD74 (mean 1.514; SD 0.397; p = 0.0097) were significantly elevated in lipedema patients, while MIF-2 expression was unaffected (mean 1.004; SD 0.358; p = 0.9718). The IHC analysis corroborated the results for CD74 expression on a cellular level. In conclusion, our results provide first evidence for a potential involvement of the MIF family, presumably via the MIF-1-CD74 axis, in lipedema.
BACKGROUND: Lipedema is a chronic disease characterized by abnormal growth of subcutaneous fatty tissue. More than 10% of women have varying degrees of lipedema. Despite the high prevalence of this pathology, to date, there are no full-fledged clinical guidelines, and only sporadic publications have devoted to this disease in the literature. AIM: To determine the level of immersion of members of the professional community in the diagnosis and treatment of lipedema. METHODS: Within the framework of the online educational event “Lipedema: 2023” held on the platform “Actual Phlebology” on 22.08.23, 74 physician participants anonymously answered 14 questions on the diagnosis and treatment of patients with lipedema. RESULTS: In this study, 83.8% of the respondents adhered to the hereditary theory of lipedema development. Only one obvious feature of lipedema, the presence of bilateral symmetrical disproportionate proliferation of adipose tissue on the extremities, was reported by the absolute majority (98.6%) of the specialists interviewed. Less than half of the professional participants noted features such as a feeling of tightness and an excessive tendency to hematoma formation with worsening of symptoms overnight. More than half of the respondents (54.1%) admitted that they were unfamiliar with the classification of lipedema. The main method of conservative treatment of lipedema was considered therapeutic exercise by 74.3% of the respondents. The most popular method of surgical treatment of lipedema is lymphatic liposuction, and which 56.8% of the participants of the professional community are ready to offer this to their patients. CONCLUSION: The professional community is not sufficiently immersed in the diagnosis and treatment of patients with lipedema. The diversity of current scientific evidence on lipedema requires that it be structured in the development of up-to-date national clinical guidelines.
Puntos clave El lipedema es una enfermedad que no suele ser conocida y por ello está infradiagnosticada. Suele confundirse con la obesidad, la celulitis y el linfedema. El diagnóstico es fundamentalmente clínico. El conocimiento de esta patología por parte de los médicos de Atención Primaria (AP) ayudará a los pacientes a conocer su enfermedad, diagnosticarlos y ofrecerles tratamiento. Los cambios de estilo de vida, la información y el apoyo psicológico son indispensables para esta patología. Hay que informar que hay asociaciones de enfermos con lipedema. El tratamiento quirúrgico puede ser una opción para mejorar la clínica de estos pacientes, aunque no suele estar cubierto por la sanidad pública.
