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International Journal of Molecular... Oct 2021Lipedema is a painful fat disorder that affects ~11% of the female population. It is characterized by bilateral, disproportionate accumulation of subcutaneous adipose... (Review)
Review
Lipedema is a painful fat disorder that affects ~11% of the female population. It is characterized by bilateral, disproportionate accumulation of subcutaneous adipose tissue predominantly in the lower body. The onset of lipedema pathophysiology is thought to occur during periods of hormonal fluctuation, such as puberty, pregnancy, or menopause. Although the identification and characterization of lipedema have improved, the underlying disease etiology remains to be elucidated. Estrogen, a key regulator of adipocyte lipid and glucose metabolism, and female-associated body fat distribution are postulated to play a contributory role in the pathophysiology of lipedema. Dysregulation of adipose tissue accumulation via estrogen signaling likely occurs by two mechanisms: (1). altered adipocyte estrogen receptor distribution (ERα/ERß ratio) and subsequent metabolic signaling and/or (2). increased release of adipocyte-produced steroidogenic enzymes leading to increased paracrine estrogen release. These alterations could result in increased activation of peroxisome proliferator-activated receptor γ (PPARγ), free fatty acid entry into adipocytes, glucose uptake, and angiogenesis while decreasing lipolysis, mitochondriogenesis, and mitochondrial function. Together, these metabolic alterations would lead to increased adipogenesis and adipocyte lipid deposition, resulting in increased adipose depot mass. This review summarizes research characterizing estrogen-mediated adipose tissue metabolism and its possible relation to excessive adipose tissue accumulation associated with lipedema.
Topics: Adipose Tissue; Animals; Estrogens; Humans; Lipedema; Receptors, Estrogen; Signal Transduction
PubMed: 34769153
DOI: 10.3390/ijms222111720 -
International Journal of Molecular... Jun 2022Lymphedema and lipedema are complex diseases. While the external presentation of swollen legs in lower-extremity lymphedema and lipedema appear similar, current... (Review)
Review
Lymphedema and lipedema are complex diseases. While the external presentation of swollen legs in lower-extremity lymphedema and lipedema appear similar, current mechanistic understandings of these diseases indicate unique aspects of their underlying pathophysiology. They share certain clinical features, such as fluid (edema), fat (adipose expansion), and fibrosis (extracellular matrix remodeling). Yet, these diverge on their time course and known molecular regulators of pathophysiology and genetics. This divergence likely indicates a unique route leading to interstitial fluid accumulation and subsequent inflammation in lymphedema versus lipedema. Identifying disease mechanisms that are causal and which are merely indicative of the condition is far more explored in lymphedema than in lipedema. In primary lymphedema, discoveries of genetic mutations link molecular markers to mechanisms of lymphatic disease. Much work remains in this area towards better risk assessment of secondary lymphedema and the hopeful discovery of validated genetic diagnostics for lipedema. The purpose of this review is to expose the distinct and shared (i) clinical criteria and symptomatology, (ii) molecular regulators and pathophysiology, and (iii) genetic markers of lymphedema and lipedema to help inform future research in this field.
Topics: Adipose Tissue; Edema; Fibrosis; Humans; Lipedema; Lymphedema
PubMed: 35743063
DOI: 10.3390/ijms23126621 -
Obesity (Silver Spring, Md.) Oct 2019Lipedema is a chronic progressive disease characterized by abnormal fat distribution resulting in disproportionate, painful limbs. It almost exclusively affects women,... (Review)
Review
Lipedema is a chronic progressive disease characterized by abnormal fat distribution resulting in disproportionate, painful limbs. It almost exclusively affects women, leading to considerable disability, daily functioning impairment, and psychosocial distress. Literature shows both scarce and conflicting data regarding its prevalence. Lipedema has been considered a rare entity by several authors, though it may be a far more frequent condition than thought. Despite the clinical impact on women's health, lipedema is in fact mostly unknown, underdiagnosed, and too often misdiagnosed with other similarly presenting diseases. Polygenic susceptibility combined with hormonal, microvascular, and lymphatic disorders may be partly responsible for its development. Furthermore, consistent information on lipedema pathophysiology is still lacking, and an etiological treatment is not yet available. Weight loss measures exhibit minimal effect on the abnormal body fat distribution, resulting in eating disorders, increased obesity risk, depression, and other psychological complaints. Surgical techniques, such as liposuction and excisional lipectomy, represent therapeutic options in selected cases. This review aims to outline current evidence regarding lipedema epidemiology, pathophysiology, clinical presentation, differential diagnosis, and management. Increased awareness and a better understanding of its clinical presentation and pathophysiology are warranted to enable clinicians to diagnose and treat affected patients at an earlier stage.
Topics: Body Fat Distribution; Diagnosis, Differential; Female; Humans; Lipectomy; Lipedema; Male; Obesity
PubMed: 31544340
DOI: 10.1002/oby.22597 -
Journal of Preventive Medicine and... Jun 2022A clinical research requires a systematic approach with diligent planning, execution and sampling in order to obtain reliable and validated results, as well as an... (Review)
Review
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.
Topics: Humans; Research Design
PubMed: 36479476
DOI: 10.15167/2421-4248/jpmh2022.63.2S3.2769 -
Journal of Preventive Medicine and... Jun 2022Animal 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... (Review)
Review
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.
Topics: Humans; Rats; Mice; Animals; Animal Experimentation; Research Design
PubMed: 36479489
DOI: 10.15167/2421-4248/jpmh2022.63.2S3.2768 -
International Wound Journal Dec 2018Lipoedema is a rare painful disorder of the adipose tissue. It essentially affects females and is often misdiagnosed as lymphoedema or obesity. It is globally... (Comparative Study)
Comparative Study Review
Lipoedema is a rare painful disorder of the adipose tissue. It essentially affects females and is often misdiagnosed as lymphoedema or obesity. It is globally misdiagnosed or underdiagnosed, and the literature is lacking appropriate guidance to assist clinicians towards this diagnosis. However, the need to recognise this disorder as a unique entity has important implications to establish proper treatment and, therefore, its tremendous effect on patients. Early diagnosis and treatment can turn these patients' lives upside down. The aim of this review is to focus on the clinical guidance, differential diagnosis, and management strategies. In addition, other aspects of lipoedema, including epidemiology and pathogenesis, are also being discussed here. Lipoedema is distinct from obesity and distinct from lymphoedema, although it might progress to involve the venous and lymphatic system (venolipedema or lympholipedema or both). Late diagnosis can leave the patient debilitated. Management of lipoedema includes weight loss, control of oedema, complex decongestive physiotherapy, liposuction, and laser-assisted lipolysis. However; there are increasing reports on tumescent liposuction as the preferred surgical option with long-lasting results. The role of more randomised controlled studies to further explore the management of this clinical entity remains promising.
Topics: Diagnostic Errors; Female; Humans; Lipedema; Lymphedema; Male
PubMed: 29956468
DOI: 10.1111/iwj.12949 -
Dermatologie (Heidelberg, Germany) Mar 2023Edema of the lower extremities is always associated with a pathological condition that should be treated, especially in patients with chronic wounds. Because the... (Review)
Review
Edema of the lower extremities is always associated with a pathological condition that should be treated, especially in patients with chronic wounds. Because the underlying causes of edema can vary greatly and sometimes be complex, clinical and, if necessary, various diagnostic tests should also be performed. Often, a suspected clinical diagnosis can already be made after clinical inspection with testing of Stemmer's and Godet's signs. Sonographic examination should then be performed as the next diagnostic test. Although measurement techniques such as water plethysmography are currently considered gold standard for volume measurements, they are very complex and prone to error, so that they are rarely used in clinical routine today. In summary, it is recommended to perform a clinical examination, if possible in combination with sonography, for edema diagnosis. Especially at the beginning of the decongestion phase, regular circumferential measurements should be performed and documented. This documentation is of high relevance for evaluation of therapeutic success.
Topics: Humans; Leg; Edema; Lower Extremity; Physical Examination; Diagnosis, Differential
PubMed: 36484790
DOI: 10.1007/s00105-022-05082-6 -
Current Obesity Reports Dec 2023This 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... (Review)
Review
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. 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.
Topics: Humans; Lipedema; Diet, Ketogenic; Obesity; Treatment Outcome; Anti-Inflammatory Agents
PubMed: 37924422
DOI: 10.1007/s13679-023-00536-x