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Lipedema is a pathology of adipose tissue, still of unclear etiology and challenging to diagnose. For these reasons, a therapeutic approach is also complex and sometimes controversial. The inflammation state present in lipedema can be limited by controlling the glycemic peaks. Specifically, the ketogenic diet (KD) seems to have the right conditions to be effective. Herein, we reported a subject diagnosed with lipedema who, with only KD nutritional intervention, achieved a significant weight loss (−41 Kg), with a net decrease in body circumferences, and also reporting an improvement in pain, and therefore in the overall quality of life. She refused other types of intervention and kept KD for two years. This case could represent the first step to organize a KD nutritional protocol specifically applied to lipedema.

Adipocytes express various enzymes, such as aldo-keto reductases (AKR1C), 11β-hydroxysteroid dehydrogenase (11β-HSD), aromatase, 5α-reductases, 3β-HSD, and 17β-HSDs involved in steroid hormone metabolism in adipose tissues. Increased activity of AKR1C enzymes and their expression in mature adipocytes might indicate the association of these enzymes with subcutaneous adipose tissue deposition. The inactivation of androgens by AKR1C enzymes increases adipogenesis and fat mass, particularly subcutaneous fat. AKR1C also causes reduction of estrone, a weak estrogen, to produce 17β-estradiol, a potent estrogen and, in addition, it plays a role in progesterone metabolism. Functional impairments of adipose tissue and imbalance of steroid biosynthesis could lead to metabolic disturbances. In this review, we will focus on the enzymes involved in steroid metabolism and fat tissue deposition.

Dercum's disease (DD), also described as adiposis dolorosa, is a poorly understood and rare adipose tissue disorder involving obesity and painful adipose tissue masses. Patients may have associated bruising and constitutional symptoms such as fatigue, difficulty concentrating, and sleep disturbance. DD was initially described in 1888 by Francis Xavier Dercum, and was classified into four subtypes, including generalized diffuse, generalized nodular, localized nodular, and juxta-articular subtypes. While this disease has been described for more than 130 years, its etiology and treatment remain elusive. We describe a case of a patient with DD who presented to Ochsner Medical Center, New Orleans, LA, for evaluation of treatment options. We review current knowledge on this rare disease and data on modern treatment methods.

Human aldo-keto reductase family 1C1 (AKR1C1) is an important enzyme involved in human hormone metabolism, which is mainly responsible for the metabolism of progesterone in the human body. AKR1C1 is highly expressed and has an important relationship with the occurrence and development of various diseases, especially some cancers related to hormone metabolism. Nowadays, many inhibitors against AKR1C1 have been discovered, including some synthetic compounds and natural products, which have certain inhibitory activity against AKR1C1 at the target level. Here we briefly reviewed the physiological and pathological functions of AKR1C1 and the relationship with the disease, and then summarized the development of AKR1C1 inhibitors, elucidated the interaction between inhibitors and AKR1C1 through molecular docking results and existing co-crystal structures. Finally, we discussed the design ideals of selective AKR1C1 inhibitors from the perspective of AKR1C1 structure, discussed the prospects of AKR1C1 in the treatment of human diseases in terms of biomarkers, pre-receptor regulation and single nucleotide polymorphisms, aiming to provide new ideas for drug research targeting AKR1C1.

Lipedema, a poorly understood chronic disease of adipose hyper-deposition, is often mistaken for obesity and causes significant impairment to mobility and quality-of-life. To identify molecular mechanisms underpinning lipedema, we employed comprehensive omics-based comparative analyses of whole tissue, adipocyte precursors (adipose-derived stem cells (ADSCs)), and adipocytes from patients with or without lipedema.

Lipomas are the most common soft tissue tumors and are malignant in only 1% of cases. Lipomatosis is defined as the presence of multiple benign lipomas on the body, without lipoatrophy. Their impact on quality of life is significant. Different entities have been described such as symmetrical multiple lipomatosis (MSL), also called Madelung's disease and familial multiple lipomatosis (FML). MSL occurs preferentially in men (but also women) who are alcohol abuser. There are different subtypes of the disease, the most classic of which affects the upper body and the nuchal region with a buffalo hump appearance. A metabolic component with obesity is frequent. In contrast to Dercum's disease, there is no pain. SAOS, complications of the metabolic syndrome and of alcohol abuse including cancers, may be associated and should be screened. FML has been little described in the literature since Brodie's first report in 1846. FML occurs preferentially in the third decade but equally in women and men. Its autosomal dominant component is classically accepted with variable penetrance within the same family. Association with naevi, angiomas, polyneuropathies and with gastrointestinal comorbidities has been reported. Interestingly, and in contrast with most lipodystrophy disorders, the patients show an insulin sensitivity profile. A better understanding of the underlying pathophysiological mechanisms would open up avenues on therapeutic research, since treatments are only symptomatic to date.

Lipedema adalah penyakit kronis dan progresif yang dapat menyebabkan kecacatan yang cukup besar, gangguan fungsi sehari-hari, dan gangguan psikososial. Ciri khasnya adalah distribusi lemak tubuh yang tidak proporsional pada ekstremitas Lipedema seringkali tidak dikenali atau salah didiagnosis; Meskipun prevalensi diperkirakan 10% pada keseluruhan populasi wanita, penyebabnya masih belum diketahui. Penelitian bertujuan untuk mengetahui lebih lanjut mengenai penyakit Lipedema secara komprehensif. Literature  review tipe  naratif dari berbagai jurnal internasional. Penulisan ini berdasarkan hasil pencarian sumber literature Google Cendekia dan NCBI Pubmed dengan criteria inklusi penelitian yang dilakukan dengan batas waktu 10 tahun kebelakang dengan rentang waktu 2010 - 2020. Kata kunci yang digunakan untuk mencari literature review adalah “lipedema”, “obesity”, “oedema” dan “lipid”. Literature searching ini menghasilkan 2.509 artikel kemudian dipilih 21 artikel yang kemudian digunakan untuk dianalisis menggunakan systemic literature review. Evaluasi diagnostik dasar lipedema terdiri dari anamnesis, inspeksi, dan palpasi, dengan perhatian khusus pada manifestasi yang tercantum sebagai kriteria klinis. Metode diagnostik lainnya adalah, dual-energy X-ray absorptiometri (DEXA), yang mengukur komposisi tubuh regional, memberikan informasi penghitungan dan distribusi tentang lemak total dan regional, dan massa tulang. Terkait terapi yang dapat diberikan terdiri dari perawatan konservatif dan bedah. Pendekatan terapi secara multidisplin ilmu merupakan pilihan terbaik pada kondisi lipedema saat ini, serta terdapat banyak hal yang tidak diketahui mengenai Lipedema.

Adipose tissue, once thought to be an inert receptacle for energy storage, is now recognized as a complex tissue with multiple resident cell populations which actively collaborate in response to diverse local and systemic metabolic, thermal, and inflammatory signals. A key participant in adipose tissue homeostasis that has only recently captured broad scientific attention is the lymphatic vasculature. The lymphatic system's role in lipid trafficking and mediating inflammation makes it a natural partner in the regulation of adipose tissue, and evidence supporting a bidirectional relationship between lymphatics and adipose tissue has accumulated in recent years. Obesity is now understood to impair lymphatic function, while altered lymphatic function results in aberrant adipose tissue deposition, though the molecular mechanisms governing these phenomena have yet to be fully elucidated. We will review our current understanding of the relationship between adipose tissue and the lymphatic system here, focusing on known mechanisms of lymphatic-adipose cross-talk.

Purpose: To discuss the status and progress of treatment of lower limb lymphedema (LLL) after gynecological cancer treatment. Common gynecological malignancies include endometrial cancer, cervical cancer, ovarian cancer, and vulvar cancer. LLL is one of the common complications after gynecological cancer treatment. LLL is one of the common complications after gynecological cancer treatment, which seriously affects patients' quality of life. Methods: We searched the Medline database for literature on LLL after gynecological oncology treatment, reviewed the incidence and risk factors for LLL in different gynecological malignancies, and summarized advances in the prevention and treatment of LLL after gynecological malignancy treatment. Finally, we review data-based approaches for the treatment of LLL and discuss experimental therapies currently in development. Results: Treatment of LLL is usually combined, conservative, and surgical. Complete decongestive therapy is the gold standard for the treatment of LLL. Prevention and treatment of lymphedema of the lower extremities are important for patients with gynecological cancers. Conclusion: Clinicians should be aware of the prevention and treatment of LLL, with a precise diagnosis and effective intervention at an early stage to delay its progression and improve patients' quality of life.

Breast cancer treatment-related lymphedema (BCRL) is a common co-morbidity of breast cancer therapies, yet factors that contribute to BCRL progression remain incompletely characterized. We investigated whether magnetic resonance imaging (MRI) measures of subcutaneous adipose tissue were uniquely elevated in women with BCRL.

Diffuse Lipomatosis is a dermatological lesion consisting of a poorly circumscribed, infiltrative overgrowth of mature adipose tissue that usually affects the trunk and the extremities. The lesions in the Tuberous Sclerosis Complex (TSC) are usually hamartomatous in nature, but lesions arising from adipocytes are rare. There are only three previous reports of association of TSC with diffuse lipomatosis. Herein we present a case series of diffuse lipomatosis in three subjects with TSC and proceed to review the literature for any other reported cases. On the basis of the three index cases and identification of three more cases in the literature, we believe that there is an association of diffuse lipomatosis with TSC that has not been appreciated until now. We believe that this association in some selected cases will serve to improve diagnosis, surveillance, and management..

In mice, embryonic dermal lymphatic development is well understood and used to study gene functions in lymphangiogenesis. Notch signaling is an evolutionarily conserved pathway that modulates cell fate decisions, which has been shown to both inhibit and promote dermal lymphangiogenesis. Here, we demonstrate distinct roles for Notch4 signaling versus canonical Notch signaling in embryonic dermal lymphangiogenesis. Actively growing embryonic dermal lymphatics expressed NOTCH1, NOTCH4, and DLL4 which correlated with Notch activity. In lymphatic endothelial cells (LECs), DLL4 activation of Notch induced a subset of Notch effectors and lymphatic genes, which were distinctly regulated by Notch1 and Notch4 activation. Treatment of LECs with VEGF-A or VEGF-C upregulated Dll4 transcripts and differentially and temporally regulated the expression of Notch1 and Hes/Hey genes. Mice nullizygous for Notch4 had an increase in the closure of the lymphangiogenic fronts which correlated with reduced vessel caliber in the maturing lymphatic plexus at E14.5 and reduced branching at E16.5. Activation of Notch4 suppressed LEC migration in a wounding assay significantly more than Notch1, suggesting a dominant role for Notch4 in regulating LEC migration. Unlike Notch4 nulls, inhibition of canonical Notch signaling by expressing a dominant negative form of MAML1 (DNMAML) in Prox1+ LECs led to increased lymphatic density consistent with an increase in LEC proliferation, described for the loss of LEC Notch1. Moreover, loss of Notch4 did not affect LEC canonical Notch signaling. Thus, we propose that Notch4 signaling and canonical Notch signaling have distinct functions in the coordination of embryonic dermal lymphangiogenesis.

Current diagnostic methods for evaluating the functionality of the lymphatic vascular system usually do not provide quantitative data and suffer from many limitations including high costs, complexity, and the need to perform them in hospital settings. In this work, we present a quantitative, simple outpatient technology named LymphMonitor to quantitatively assess lymphatic function. This method is based on the painless injection of the lymphatic-specific near-infrared fluorescent tracer indocyanine green complexed with human serum albumin, using MicronJet600TM microneedles, and monitoring the disappearance of the fluorescence signal at the injection site over time using a portable detection device named LymphMeter. This technology was investigated in 10 patients with unilateral leg or arm lymphedema. After injection of a tracer solution into each limb, the signal was measured over 3 h and the area under the normalized clearance curve was calculated to quantify the lymphatic function. A statistically significant difference in lymphatic clearance in the healthy versus the lymphedema extremities was found, based on the obtained area under curves of the normalized clearance curves. This study provides the first evidence that the LymphMonitor technology has the potential to diagnose and monitor the lymphatic function in patients.

Lymphatic vessels have crucial roles in the regulation of interstitial fluids, immune surveillance, and the absorption of dietary fat in the intestine. Lymphatic function is also closely related to the pathogenesis of various disease states such as inflammation, lymphedema, endometriosis, liver dysfunction, and tumor metastasis. Lymphangiogenesis, the formation of new lymphatic vessels from pre-existing lymphatic vessels, is a critical determinant in the above conditions. Although the effect of growth factors on lymphangiogenesis is well-characterized, and biologically active lipids are known to affect smooth muscle contractility and vasoaction, there is accumulating evidence that biologically active lipids are also important inducers of growth factors and cytokines that regulate lymphangiogenesis. This review discusses recent advances in our understanding of biologically active lipids, including arachidonic acid metabolites, sphingosine 1-phosphate, and lysophosphatidic acid, as regulators of lymphangiogenesis, and the emerging importance of the lymphangiogenesis as a therapeutic target.

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.

Dr. Allen and Dr. Hines pioneered and first described lipedema in the 1940s, a common subcutaneous adipose tissue disorder characterized as enlargement of both lower extremities. Lipedema is not edema; it is a genetically determined disturbance in adipose tissue mass and adipose tissue distribution.[1][2][3][4] In 1951 a second seminal paper provided more description of lipedema. Fat distribution involves lower extremities, upper arms, hips, buttocks, thighs sparing trunks, and feet.[2] Lower extremities are characterized by pain, easy bruisability, firm subcutaneous nodules of adipose tissue, and resistance of fat to traditional diet and exercise.[5][6]

Lipoedema UK welcomed our involvement with NICE and the opportunity to comment on noncosmetic liposuction (NCL) as a proposed interventional procedure for chronic lipoedema. In response, we have been proactive in capturing the views and experiences of individuals in the UK living with lipoedema and from those who have undergone non-cosmetic liposuction.

Bone is one of the preferential target organs of cancer metastasis. Bone metastasis is associated with various complications, of which bone pain is most common and debilitating. The cancer-associated bone pain (CABP) is induced as a consequence of increased neurogenesis, reprogramming and axonogenesis of sensory nerves (SNs) in harmony with sensitization and excitation of SNs in response to the tumor microenvironment created in bone. Importantly, CABP is associated with increased mortality, of which precise cellular and molecular mechanism remains poorly understood. Bone is densely innervated by autonomic nerves (ANs) (sympathetic and parasympathetic nerves) and SNs. Recent studies have shown that the nerves innervating the tumor microenvironment establish intimate communications with tumors, producing various stimuli for tumors to progress and disseminate. In this review, our current understanding of the role of SNs innervating bone in the pathophysiology of CABP will be overviewed. Then the hypothesis that SNs facilitate cancer progression in bone will be discussed in conjunction with our recent findings that SNs play an important role not only in the induction of CABP but also the progression of bone metastasis using a preclinical model of CABP. It is suggested that SNs are a critical component of the bone microenvironment that drives the vicious cycle between bone and cancer to progress bone metastasis. Suppression of the activity of bone-innervating SNs may have potential therapeutic effects on the progression of bone metastasis and induction of CABP.

The article presents a case of a 17-year-old female who was presented to a clinic due to a 2-year history of unilateral swelling of her left lower extremity. She also reported a poorly healed ankle sprain on her affected extremity. Also cited are her differential diagnosis like lipidema and lymphatic and venous etiologies of edema, and her clinical diagnosis of lymphedema praecox.

<p>Bei 640 Patientinnen einer Fachklinik für operative Lymphologie erfolgte mittels Fragebogen der Deutschen Schmerzgesellschaft e. V. eine Befragung. Neben Fragen zum Schmerz und zur Schmerzcharakteristik wurden gleichzeitig noch demografische Daten miterhoben. Es ergab sich, dass nur bei etwas über 50 % eine echte Adipositas nachgewiesen werden konnte. Lipödem und Adipositas müssen als unabhängige Krankheitsbilder gewertet werden. Der Schmerz wurde überwiegend als drückend und ziehend empfunden. Attribute wie klopfend oder pochend, passend zu einer akuten Entzündung, erfuhren die Wertung „nicht zutreffend“. Die Beschwerdesymptomatik war unabhängig vom BMI, der bei der Lipohyperplasie dolorosa nur bedingt verwertbar ist. Insgesamt ist das Leitsymptom „Schmerz“ sehr facettenreich, das angeborene, nicht erworbene Lipödemfett der Extremitäten führt zu einer deutlichen Beeinträchtigung der Aktivitäten sowohl allgemein als auch im Freizeitbereich. Die durch den G-BA initiierte Studie muss daher kritisch gesehen werden. Da bislang keine objektivierbaren Befunde beim Lipödem erhoben werden können, ist eine subtile Befragung betroffener Patientinnen zur Diagnosestellung notwendig.</p>