The Expression of Adipogenic Marker Is Significantly Increased in Estrogen-Treated Lipedema Adipocytes Differentiated from Adipose Stem Cells In Vitro.

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 ERß), 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 ERß 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.

National survey of patient symptoms and therapies among 707 women with a lipedema phenotype in the United States.

BACKGROUND: National survey data exploring the patient experience with lipedema are lacking. METHODS: We conducted national surveys from 2016 to 2022 of women with lipedema as well as female controls. Surveys collected information on symptomatology, pain, and therapies. We performed logistic regression comparing symptoms among those with lipedema versus controls adjusting for age and BMI. RESULTS: A total of 707 women with lipedema and 216 controls completed the surveys. Those with lipedema had a mean age of 48.6 years and mean BMI of 40.9 kg/m2. Lipedema symptom onset occurred frequently at puberty (48.0%) or pregnancy (41.2%). Compared to controls, women with lipedema were more likely to report leg swelling in heat (odds ratio [OR], 66.82; 95% CI, 33.04-135.12; p < 0.0001), easy bruising (OR, 26.23; 95% CI, 15.58-44.17; p < 0.0001), altered gait (OR, 15.54; 95% CI, 7.58-31.96; p < 0.0001), flu-like symptoms (OR, 12.99; 95% CI, 4.27-39.49; p < 0.0001), joint hypermobility (OR, 12.88; 95% CI, 6.68-24.81; p < 0.0001), cool skin (OR, 12.21; 95% CI, 5.20-28.69; p < 0.0001), varicose veins (OR, 11.29; 95% CI, 6.71-18.99; p < 0.0001), and fatigue (OR, 9.59; 95% CI, 6.10-15.09; p < 0.0001). Additionally, 70.3% had upper arm involvement, 21.2% reported foot swelling, and 16.6% reported foot pain. Most (52.2%) reported no symptom improvement with diet or exercise. Common therapies used included compression therapy (45.0%), gastric bypass (15.7%), and lower-extremity liposuction (14.0%). CONCLUSION: In a large, national, symptom survey, women with lipedema reported excess pain, swelling, and fat in the legs along with numerous symptoms beyond those classically described. Symptom responses to common therapies remain understudied.

Enhanced Angiogenesis in HUVECs Preconditioned with Media from Adipocytes Differentiated from Lipedema Adipose Stem Cells In Vitro.

Lipedema is a connective tissue disorder characterized by increased dilated blood vessels (angiogenesis), inflammation, and fibrosis of the subcutaneous adipose tissue. This project aims to gain insights into the angiogenic processes in lipedema using human umbilical vein endothelial cells (HUVECs) as an in vitro model. HUVECs were cultured in conditioned media (CM) collected from healthy (non-lipedema, AQH) and lipedema adipocytes (AQL). The impacts on the expression levels of multiple endothelial and angiogenic markers [CD31, von Willebrand Factor (vWF), angiopoietin 2 (ANG2), hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMPs), NOTCH and its ligands] in HUVECs were investigated. The data demonstrate an increased expression of CD31 and ANG2 at both the gene and protein levels in HUVECs treated with AQL CM in 2D monolayer and 3D cultures compared to untreated cells. Furthermore, the expression of the vWF, NOTCH 4, and DELTA-4 genes decreased. In contrast, increased VEGF, MMP9, and HGF gene expression was detected in HUVECs treated with AQL CM cultured in a 2D monolayer. In addition, the results of a tube formation assay indicate that the number of formed tubes increased in lipedema-treated HUVECs cultured in a 2D monolayer. Together, the data indicate that lipedema adipocyte-CM promotes angiogenesis through paracrine-driven mechanisms.

Genome-wide association study of a lipedema phenotype among women in the UK Biobank identifies multiple genetic risk factors.

Lipedema is a common disorder characterized by excessive deposition of subcutaneous adipose tissue (SAT) in the legs, hips, and buttocks, mainly occurring in adult women. Although it appears to be heritable, no specific genes have yet been identified. To identify potential genetic risk factors for lipedema, we used bioelectrical impedance analysis and anthropometric data from the UK Biobank to identify women with and without a lipedema phenotype. Specifically, we identified women with both a high percentage of fat in the lower limbs and a relatively small waist, adjusting for hip circumference. We performed a genome-wide association study (GWAS) for this phenotype, and performed multiple sensitivity GWAS. In an independent case/control study of lipedema based on strict clinical criteria, we attempted to replicate our top hits. We identified 18 significant loci (p < 5 × 10-9), several of which have previously been identified in GWAS of waist-to-hip ratio with larger effects in women. Two loci (VEGFA and GRB14-COBLL1) were significantly associated with lipedema in the independent replication study. Follow-up analyses suggest an enrichment of genes expressed in blood vessels and adipose tissue, among other tissues. Our findings provide a starting point towards better understanding the genetic and physiological basis of lipedema.

Subcutaneous Adipose Tissue Edema in Lipedema Revealed by Noninvasive 3T MR Lymphangiography.

BACKGROUND: Lipedema exhibits excessive lower-extremity subcutaneous adipose tissue (SAT) deposition, which is frequently misidentified as obesity until lymphedema presents. MR lymphangiography may have relevance to distinguish lipedema from obesity or lymphedema. HYPOTHESIS: Hyperintensity profiles on 3T MR lymphangiography can identify distinct features consistent with SAT edema in participants with lipedema. STUDY TYPE: Prospective cross-sectional study. SUBJECTS: Participants (48 females, matched for age [mean = 44.8 years]) with lipedema (n = 14), lipedema with lymphedema (LWL, n = 12), cancer treatment-related lymphedema (lymphedema, n = 8), and controls without these conditions (n = 14). FIELD STRENGTH/SEQUENCE: 3T MR lymphangiography (nontracer 3D turbo-spin-echo). ASSESSMENT: Review of lymphangiograms in lower extremities by three radiologists was performed independently. Spatial patterns of hyperintense signal within the SAT were scored for extravascular (focal, diffuse, or not apparent) and vascular (linear, dilated, or not apparent) image features. STATISTICAL TESTS: Interreader reliability was computed using Fleiss Kappa. Fisher's exact test was used to evaluate the proportion of image features between study groups. Multinomial logistic regression was used to assess the relationship between image features and study groups. The odds ratio (OR) and 95% confidence interval (CI) of SAT extravascular and vascular features was reported in groups compared to lipedema. The threshold of statistical significance was P < 0.05. RESULTS: Reliable agreement was demonstrated between three independent, blinded reviewers (P < 0.001). The frequency of SAT hyperintensities in participants with lipedema (36% focal, 36% diffuse), LWL (42% focal, 33% diffuse), lymphedema (62% focal, 38% diffuse), and controls (43% focal, 0% diffuse) was significantly distinct. Compared with lipedema, SAT hyperintensities were less frequent in controls (focal: OR = 0.63, CI = 0.11-3.41; diffuse: OR = 0.05, CI = 0.00-1.27), similar in LWL (focal: OR = 1.29, CI = 0.19-8.89; diffuse: OR = 1.05, CI = 0.15-7.61), and more frequent in lymphedema (focal: OR = 9.00, CI = 0.30-274.12; diffuse: OR = 5.73, CI = 0.18-186.84). DATA CONCLUSION: Noninvasive MR lymphangiography identifies distinct signal patterns indicating SAT edema and lymphatic load in participants with lipedema. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 1.

Dietary supplements for obesity.

Obesity and associated complications including diabetes, cardiometabolic dysfunction, disability, malignancy and premature mortality are considered epidemic. Research on obesity is therefore of worldwide importance. The development of obesity is a multifactorial phenomenon with contributions from biological, behavioral, genetic and environmental factors. Obesity and its associated issues require various lifestyle modifications and treatment options such medication, exercise, diet, surgery, pharmacological therapy and dietary supplements. Dietary supplements are considered an attractive alternative to traditional therapy due to their low toxicity profile and their accessibility to the general population. Dietary supplements may include one or more dietary ingredients. In this narrative review, we analyze the effects on obesity and obesity-related issues of various natural components. For example, there are a myriad of supplements that have been used as dietary supplements for weight loss such as minerals, vitamins, amino acids, metabolites, herbs, and plant extracts. This narrative review aims to present the benefits and side-effects of several ingredients of dietary supplements for weight loss and treatment of obesity. In particular, the mechanism of action, results of clinical trials, and possible side effects will be presented for the following ingredients: ß-Glucans, bitter orange, calcium, vitamin D, chitosan, chromium, cocoa, coleus forskohlii, conjugate linoleic acid, ephedra sinica, fucoxanthin, garcinia cambogia, glucomannan, green coffee, green tea, guar gum, raspberry, hoodia gordonii, irvingia gabonensis, phenylpropylamine, pyruvate, white kidney bean.

Modern vision of the Mediterranean diet.

The Mediterranean diet is the most well-known and researched dietary pattern worldwide. It is characterized by the consumption of a wide variety of foods, such as extra-virgin olive oil (EVOO), legumes, cereals, nuts, fruits, vegetables, dairy products, fish, and wine. Many of these foods provide several phytonutrients, among which polyphenols and vitamins play an important role. Data from several studies have strongly established that nutrition is a key factor in promoting a healthy lifestyle and preventing many chronic diseases. In particular, a large number of studies have established the protective effects of the Mediterranean diet against several chronic diseases, among which are diabetes, cardiovascular diseases, cancer, aging disorders, and against overall mortality. Animal and human translational studies have revealed the biological mechanisms regulating the beneficial effects of the traditional Mediterranean diet. Indeed, several studies demonstrated that this nutritional pattern has lipid-lowering, anticancer, antimicrobial, and anti-oxidative effects. Moreover, the Mediterranean diet is considered environmentally sustainable. In this review, we describe the composition of the Mediterranean diet, assess its beneficial effects, and analyze their epigenomic, genomic, metagenomic, and transcriptomic aspects. In the future it will be important to continue exploring the molecular mechanisms through which the Mediterranean diet exerts its protective effects and to standardize its components and serving sizes to understand more precisely its effects on human health.

Methodology for clinical research.

A clinical research requires a systematic approach with diligent planning, execution and sampling in order to obtain reliable and validated results, as well as an understanding of each research methodology is essential for researchers. Indeed, selecting an inappropriate study type, an error that cannot be corrected after the beginning of a study, results in flawed methodology. The results of clinical research studies enhance the repertoire of knowledge regarding a disease pathogenicity, an existing or newly discovered medication, surgical or diagnostic procedure or medical device. Medical research can be divided into primary and secondary research, where primary research involves conducting studies and collecting raw data, which is then analysed and evaluated in secondary research. The successful deployment of clinical research methodology depends upon several factors. These include the type of study, the objectives, the population, study design, methodology/techniques and the sampling and statistical procedures used. Among the different types of clinical studies, we can recognize descriptive or analytical studies, which can be further categorized in observational and experimental. Finally, also pre-clinical studies are of outmost importance, representing the steppingstone of clinical trials. It is therefore important to understand the types of method for clinical research. Thus, this review focused on various aspects of the methodology and describes the crucial steps of the conceptual and executive stages.

Metabolomics application for the design of an optimal diet.

Precision nutrition is an emerging branch of nutrition science that aims to use modern omics technologies (genomics, proteomics, and metabolomics) to assess an individual's response to specific foods or dietary patterns and thereby determine the most effective diet or lifestyle interventions to prevent or treat specific diseases. Metabolomics is vital to nearly every aspect of precision nutrition. It can be targeted or untargeted, and it has many applications. Indeed, it can be used to comprehensively characterize the thousands of chemicals in foods, identify food by-products in human biofluids or tissues, characterize nutrient deficiencies or excesses, monitor biochemical responses to dietary interventions, track long- or short-term dietary habits, and guide the development of nutritional therapies. Indeed, metabolomics can be coupled with genomics and proteomics to study and advance the field of precision nutrition. Integrating omics with epidemiological and clinical data will begin to define the beneficial effects of human food metabolites. In this review, we present the metabolome and its relationship to precision nutrition. Moreover, we describe the different techniques used in metabolomics and present how metabolomics has been applied to advance the field of precision nutrition by providing notable examples and cases.

Physical activity for health.

Physical activity plays a substantial role in maintaining people's good health and mental wellbeing, but that is not all: not only it positively affects the individuals' mental and physical health, but a lack of physical exercise exerts a negative impact also on the overall economy of a nation. In addition, physical inactivity not only increases the risk of non-communicable diseases (NCD), but also contributes significantly to the increased morbidity and mortality in patients suffering from these diseases. On the contrary, physical activity reduces the risk of NCDs - such as cardiovascular diseases, type 2 diabetes, and cancer - in a dose-dependent manner; regular exercise is also associated with many health benefits and delayed mortality. However, understanding the role of physical activity in modern society and creating an awareness in the general population is one of the most important tasks of health and recreation promoters. Correspondingly, there is a dire need to enhance our knowledge, perception, and awareness of physical activity and its impacts on an individual's health, ultimately contributing to developing a healthy society. The current review will focus on the health benefits of the two most widely studied modifiable lifestyle risk factors, physical activity and diet, focusing particularly on the Mediterranean diet.

Polymorphisms, diet and nutrigenomics.

Every human being possesses an exclusive nutritional blueprint inside their genes. Bioactive food components and nutrients affect the expression of such genes. Nutrigenomics is the science that analyzes gene-nutrient interactions (nutrigenetics), which can lead to the development of personalized nutritional recommendations to maintain optimal health and prevent disease. Genomic diversity among various ethnic groups might affect nutrients bioavailability as well as their metabolism. Nutrigenomics combines different branches of science including nutrition, bioinformatics, genomics, molecular biology, molecular medicine, and epidemiology. Genes regulate intake and metabolism of different nutrients, while nutrients positively or negatively influence the expression of a number of genes; testing of specific genetic polymorphisms may therefore become a useful tool to manage weight loss and to fully understand gene-nutrient interactions. Indeed, several approaches are used to study gene-nutrient interactions: epigenetics, the study of genome modification not related to changes in nucleotide sequence; transcriptomics, the study of tissue-specific and time-specific RNA transcripts; proteomics, the study of proteins involved in biological processes; and metabolomics, the study of changes of primary and secondary metabolites in body fluids and tissues. Hence, the use of nutrigenomics to improve and optimize a healthy, balanced diet in clinical settings could be an effective approach for long-term lifestyle changes that might lead to consistent weight loss and improve quality of life.

Ethical considerations regarding animal experimentation.

Animal experimentation is widely used around the world for the identification of the root causes of various diseases in humans and animals and for exploring treatment options. Among the several animal species, rats, mice and purpose-bred birds comprise almost 90% of the animals that are used for research purpose. However, growing awareness of the sentience of animals and their experience of pain and suffering has led to strong opposition to animal research among many scientists and the general public. In addition, the usefulness of extrapolating animal data to humans has been questioned. This has led to Ethical Committees' adoption of the 'four Rs' principles (Reduction, Refinement, Replacement and Responsibility) as a guide when making decisions regarding animal experimentation. Some of the essential considerations for humane animal experimentation are presented in this review along with the requirement for investigator training. Due to the ethical issues surrounding the use of animals in experimentation, their use is declining in those research areas where alternative in vitro or in silico methods are available. However, so far it has not been possible to dispense with experimental animals completely and further research is needed to provide a road map to robust alternatives before their use can be fully discontinued.

Validating methods for testing natural molecules on molecular pathways of interest in silico and in vitro.

Differentially expressed genes can serve as drug targets and are used to predict drug response and disease progression. In silico drug analysis based on the expression of these genetic biomarkers allows the detection of putative therapeutic agents, which could be used to reverse a pathological gene expression signature. Indeed, a set of bioinformatics tools can increase the accuracy of drug discovery, helping in biomarker identification. Once a drug target is identified, in vitro cell line models of disease are used to evaluate and validate the therapeutic potential of putative drugs and novel natural molecules. This study describes the development of efficacious PCR primers that can be used to identify gene expression of specific genetic pathways, which can lead to the identification of natural molecules as therapeutic agents in specific molecular pathways. For this study, genes involved in health conditions and processes were considered. In particular, the expression of genes involved in obesity, xenobiotics metabolism, endocannabinoid pathway, leukotriene B4 metabolism and signaling, inflammation, endocytosis, hypoxia, lifespan, and neurotrophins were evaluated. Exploiting the expression of specific genes in different cell lines can be useful in in vitro to evaluate the therapeutic effects of small natural molecules.

Dietary supplements for lipedema.

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.

Indications of Peripheral Pain, Dermal Hypersensitivity, and Neurogenic Inflammation in Patients with Lipedema.

Lipedema is a disease with abnormally increased adipose tissue deposition and distribution. Pain sensations have been described in the clinical evaluation of lipedema, but its etiology remains poorly understood. We hypothesized that pain sensitivity measurements and ex vivo quantitation of neuronal cell body distribution in the skin would be lipedema stage-dependent, and could, thus, serve to objectively characterize neuropathic pain in lipedema. The pain was assessed by questionnaire and peripheral cutaneous mechanical sensitization (von-Frey) in lipedema (n = 27) and control (n = 23) consenting female volunteers. Dermal biopsies from (n = 11) Stages 1-3 lipedema and control (n = 10) participants were characterized for neuronal cell body and nociceptive neuropeptide calcitonin gene-related peptide (CGRP) and nerve growth factor (NGF) distribution. Stage 2 or 3 lipedema participants responded positively to von Frey sensitization in the calf and thigh, and Stage 3 participants also responded in the arm. Lipedema abdominal skin displayed reduced Tuj-1+ neuronal cell body density, compared to healthy controls, while CGRP and NGF was significantly elevated in Stage 3 lipedema tissues. Together, dermal neuronal cell body loss is consistent with hyper-sensitization in patients with lipedema. Further study of neuropathic pain in lipedema may elucidate underlying disease mechanisms and inform lipedema clinical management and treatment impact.

A Case Series of Lymphatic Injuries After Suction Lipectomy in Women with Lipedema.

BACKGROUND Lipedema is a loose connective tissue disease characterized by disproportionate subcutaneous adipose tissue hypertrophy in the extremities. There is evidence of impaired lymphatic function in women with lipedema at all stages without signs of trophic skin changes associated with hereditary or acquired lymphedema. A modification of suction lipectomy is used to treat lipedema tissue and can reduce pain, limb size, and limb swelling and reduce the need for compression in women with lipedema. Studies have shown that modified liposuction can improve quality of life and mobility. There are no reports of lymphatic injury after suction lipectomy in patients with lipedema in PubMed indexed journals. CASE REPORT Three women with lipedema who had no prior venous or lymphatic disease developed new-onset symptomatic International Society of Lymphology (ISL) Stage 2 or 3 lymphedema and skin and tissue changes within 6 months to 1 year after suction lipectomy for lipedema tissue on the legs. Each of the 3 women had their surgeries performed using different suction devices and under different types of anesthesia. Two of the lymphatic injury cases had subsequent nuclear lymphoscintigrams that confirmed impaired lymphatic function. CONCLUSIONS We report 3 cases of women with lymphatic injuries after modified suction lipectomy to treat lipedema. Clinical history, exams, and confirmatory studies support the assessment that suction lipectomy caused newly-manifested signs and symptoms of lymphedema. Further study is needed to determine the risk of permanent lymphatic injury with suction lipectomy in larger numbers of lipedema patients.

Lymphatic function and anatomy in early stages of lipedema.

OBJECTIVE: Lipedema is an inflammatory subcutaneous adipose tissue disease that develops in women and may progress to lipolymphedema, a condition similar to lymphedema, in which lymphatic dysfunction results in irresolvable edema. Because it has been shown that dilated lymphatic vessels, impaired pumping, and dermal backflow are associated with presymptomatic, cancer-acquired lymphedema, this study sought to understand whether these abnormal lymphatic characteristics also characterize early stages of lipedema prior to lipolymphedema development. METHODS: In a pilot study of 20 individuals with Stage I or II lipedema who had not progressed to lipolymphedema, lymphatic vessel anatomy and function in upper and lower extremities were assessed by near-infrared fluorescence lymphatic imaging and compared with that of a control population of similar age and BMI. RESULTS: These studies showed that, although lower extremity lymphatic vessels were dilated and showed intravascular pooling, the propulsion rates significantly exceeded those of control individuals. Upper extremity lymphatics of individuals with lipedema were unremarkable. In contrast to individuals with lymphedema, individuals with Stage I and II lipedema did not exhibit dermal backflow. CONCLUSIONS: These results suggest that, despite the confusion in the diagnoses between lymphedema and lipedema, their etiologies differ, with lipedema associated with lymphatic vessel dilation but not lymphatic dysfunction.

A Multi-Gene Panel to Identify Lipedema-Predisposing Genetic Variants by a Next-Generation Sequencing Strategy.

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.

A Young Woman with Excessive Fat in Lower Extremities Develops Disordered Eating and Is Subsequently Diagnosed with Anorexia Nervosa, Lipedema, and Hypermobile Ehlers-Danlos Syndrome.

BACKGROUND Lipedema is a loose connective tissue disease that causes disproportionate subcutaneous fat accumulation on the extremities. As a result of the increased subcutaneous tissue accumulation, lipedema is often confused with obesity by both physicians and patients. Poor awareness and limited diagnosis of lipedema contribute to the confusion of lipedema with obesity and can lead to decreased body image acceptance. Patients with lipedema may have anorexia nervosa, an eating disorder characterized by a distortion of body image, incorrect self-identification of being overweight, restricted eating behavior, and a relentless pursuit of weight loss. CASE REPORT A young woman with disproportionate fat accumulation on the lower half of her body self-identified as having obesity. She developed restrictive eating behavior and became obsessed with weight loss, resulting in anorexia nervosa. Her disproportionate subcutaneous tissue persisted despite losing weight to reach a nadir BMI of 15 kg/m². After a decade-long struggle, her eating disorder resolved, and she maintained a healthy weight and BMI of 21.5 kg/m² but disproportionate fat remained in her lower body. She experienced increasing leg tenderness, pain, and easy bruising and was diagnosed with lipedema. CONCLUSIONS Lack of recognition of lipedema by medical professionals and the public as a weight loss-resistant disease can affect body image acceptance. Lipedema was mistaken for obesity by the young woman in this case and likely played a role in her development of an eating disorder. Eating disorders, such as anorexia nervosa, are not rare and may be more common in women with lipedema.

A 41-Year-Old Woman with Excessive Fat of the Lower Body Since Puberty with Progression to Swollen Ankles and Feet Despite Caloric Restriction, Due to Lipedema and Protein-Calorie Malnutrition: A Case of Stage 3 Lipedema.

BACKGROUND Lipedema is a common condition that presents as excessive fat deposition in the extremities, initially sparing the trunk, ankles, and feet, and is found mainly in women, usually occurring after puberty or pregnancy. Lipedema can progress to include lipo-lymphedema of the ankles and feet. This report is of a 41-year old woman with Stage 3 lipedema and lipo-lymphedema with excessive fat of the lower body since puberty, with progression to swollen ankles and feet despite dietary caloric restriction. CASE REPORT A 41-year-old woman noticed increased fat in her legs since age 12. Her weight and leg size increased until age 21, when she reached a maximum weight of 165 kg, and underwent a Roux-En-Y gastric bypass. Over 12 months, she lost 74.8 kg. Her trunk significantly reduced in weight, but her legs did not. Fifteen years later, during recovery from hysterectomy surgery, she became progressively weaker and swollen over her entire body. Laboratory test results showed hypoalbuminemia (2.0 g/dL), lymphopenia, and hypolipoproteinemia. She was diagnosed with protein and calorie malnutrition with marked gut edema requiring prolonged parenteral nutrition. After restoration of normal protein, her health returned and her pitting edema resolved, but her extremities remained enlarged. She was subsequently diagnosed with lipedema. CONCLUSIONS This report demonstrates that early and correct diagnosis of lipedema is important, as women who believe the condition is due to obesity may suffer the consequences of calorie or protein-calorie deficiency in an attempt to lose weight.