Primary hepatic pleomorphic liposarcoma: Case report and literature review / Liposarcoma pleomorfo hepático primario: presentación de un caso y revisión bibliográfica

Primary hepatic liposarcoma is an extremely rare malignant tumour derived from adipocytes and is part of the group of mesenchymal tumours. We present the case of a 43-year-old Hispanic male patient with a pleomorphic hepatic liposarcoma and absence of MDM2 gene amplification. Two years and six months after surgery, the patient is asymptomatic. The present case is the first report of this entity with positive immunohistochemical testing for p16, p53, S100, vimentin and absence of MDM2 gene amplification. (AU)

El liposarcoma hepático primario es un tumor maligno extremadamente raro, derivado de adipocitos, y forma parte del grupo de tumores mesenquimales. Presentamos el caso de un paciente masculino de 43 años con diagnóstico de liposarcoma hepático pleomorfo con ausencia de amplificación del gen MDM2. Dos años y 6 meses después de la cirugía el paciente se encuentra asintomático. El presente caso es el primer informe de esta entidad con estudio inmunohistoquímico positivo para p16, p53, S100, vimentina y ausencia de amplificación del gen MDM2. (AU)

Delivery of SIRT1 by cancer-associated adipocyte-derived extracellular vesicles regulates immune response and tumorigenesis of ovarian cancer cells

Purpose This study intends to investigate the possible molecular mechanism of immune response and tumorigenesis in ovarian cancer cells, mediated by sirtuin 1 (SIRT1)-containing extracellular vesicles (EVs) derived from cancer-associated adipocytes (CAAs) (CAA-EVs). Methods Differentially expressed genes in EVs from CAAs were screened by RNA transcriptome sequencing, and the downstream pathway was predicted in silico. The binding between SIRT1 and CD24 was investigated by luciferase activity and ChIP-PCR assays. EVs were extracted from human ovarian cancer tissue-isolated CAAs, and the internalization of CCA-EVs by ovarian cancer cells was characterized. The ovarian cancer cell line was injected into mice to establish an animal model. Flow cytometry was performed to analyze the proportions of M1 and M2 macrophages, CD8+ T, T-reg, and CD4+ T cells. TUNEL staining was used to detect cell apoptosis in the mouse tumor tissues. ELISA detection was performed on immune-related factors in the serum of mice. Results CAA-EVs could deliver SIRT1 to ovarian cancer cells, thereby affecting the immune response of ovarian cancer cells in vitro and promoting tumorigenesis in vivo. SIRT1 could transcriptionally activate the expression of CD24, and CD24 could up-regulate Siglec-10 expression. CAA-EVs-SIRT1 activated the CD24/Siglec-10 axis and promoted CD8+ T cell apoptosis, thereby promoting tumorigenesis in mice. Conclusion CAA-EVs-mediated transfer of SIRT1 regulates the CD24/Siglec-10 axis to curb immune response and promote tumorigenesis of ovarian cancer cells (AU)

LINC01119 encapsulated by cancer-associated adipocytes-derived exosomes promotes M2 polarization of macrophages to induce immune escape in ovarian cancer in a 3D co-culture cell-based model

Introduction In the present study, we sought to clarify the role of LINC01119 delivered by cancer-associated adipocytes (CAAs)-derived exosomes (CAA-Exo) and its mechanistic actions in ovarian cancer (OC). Materials and methods The expression of LINC01119 was determined in OC, and the relationship between LINC01119 expression and the prognosis of OC patients was analyzed. Besides, 3D co-culture cell models were constructed using green fluorescent protein-labeled OC cells and red fluorescent protein-labeled mature adipocytes. Mature adipocytes were co-cultured with OC cells to induce CAA. Macrophages treated with CAA-Exo were co-cultured with SKOV3 cells following ectopic expression and depletion experiments of LINC01119 and SOCS5 to detect M2 polarization of macrophages, PD-L1 level, proliferation of CD3+ T cells, and cytotoxicity of T cells to SKOV3 cells. Results LINC01119 was elevated in the plasma Exo of OC patients, which was related to shorter overall survival in OC patients. LINC01119 expression was increased in CAA-Exo, which could upregulate SOCS5 in OC. Finally, CAA-Exo carrying LINC01119 induced M2 polarization of macrophages to promote immune escape in OC, as evidenced by inhibited CD3+ T cell proliferation, increased PD-L1 level, and attenuated T cell toxicity to SKOV3 cells. Conclusion In conclusion, the key findings of the current study demonstrated the promoting effects of CAA-Exo containing LINC01119 mediating SOCS5 on M2 polarization of macrophages and immune escape in OC (AU)

Adipocytes-derived exosomal miR-122 promotes non-alcoholic fat liver disease progression via targeting Sirt1 / El miR-122 exosomal derivado de los adipocitos promueve la progresión de la enfermedad hepática por grasa no alcohólica a través de la focalización de Sirt1

Aims: Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease that affects adipose function. This study aimed to explore the function of adipocytes-derived exosomal (ADEs) miR-122 in NAFLD. Methods: A high-fat and high-fructose diet-induced rat model and a palmitic acid (PA)-induced in vitro model were established. The RNA level of miR-122 and Sirt1 was measured using qRT-PCR. The protein levels of exosome biomarkers, and lipogenesis, inflammation and fibrosis biomarkers were determined by western blotting. Cell viability and apoptosis were assessed using cell counting kit-8 and flow cytometry, respectively. Serum alanine aminotransferase, aspartate aminotransferase, total cholesterol, triglyceride levels were measured. Liver tissue damage was assessed using haematoxylin and eosin staining. The interaction between miR-122 and Sirt1 3′UTR was assessed using a luciferase reporter gene assay. Results: ADEs exhibited abundant level of miR-122 and promoted lipogenesis, impaired hepatocyte survival, enhanced liver damage and increased serum lipid levels in vivo and in vitro. Inhibition of miR-122 in ADEs alleviated NAFLD progression, lipid and glucose metabolism, liver inflammation and fibrosis both in vivo and in vitro. miR-122 binds directly to the 3′UTR of Sirt1 to suppress its expression. Moreover, Sirt1 overexpression reversed the increase in cell apoptosis, glucose and lipid metabolism, liver inflammation and fibrosis induced by ADEs in vivo and in vitro. Conclusions: The ADEs miR-122 promotes the progression of NAFLD via modulating Sirt1 signalling in vivo and in vitro. The ADEs miR-122 may be a promising diagnostic biomarker and therapeutic target for NAFLD.(AU)

Objetivos: La enfermedad del hígado graso no alcohólico (EHGNA) es una enfermedad hepática crónica que afecta a la función adiposa. Este estudio tiene como objetivo explorar la función de los exosomas derivados de los adipocitos (ADEs) miR-122 en la EHGNA. Métodos: Se estableció un modelo de rata inducido por una dieta alta en grasas y fructosa y un modelo in vitro inducido por ácido palmítico (AP). Se midió el nivel de ARN de miR-122 y Sirt1 mediante qRT-PCR. Los niveles de proteína de los biomarcadores de exosomas y los biomarcadores de lipogénesis, inflamación y fibrosis se determinaron mediante western blotting. La viabilidad celular y la apoptosis se evaluaron mediante el kit de recuento de células-8 y la citometría de flujo, respectivamente. Se midieron los niveles séricos de alanina aminotransferasa, aspartato aminotransferasa, colesterol total y triglicéridos. El daño tisular del hígado se evaluó mediante tinción con hematoxilina y eosina. La interacción entre miR-122 y Sirt1 3’UTR se evaluó mediante un ensayo de gen reportero de luciferasa. Resultados: Los ADEs mostraron un nivel abundante de miR-122 y promovieron la lipogénesis, perjudicaron la supervivencia de los hepatocitos, potenciaron el daño hepático y aumentaron los niveles de lípidos séricos in vivo e in vitro. La inhibición de miR-122 en los ADEs alivió la progresión de la EHGNA, el metabolismo de los lípidos y la glucosa, la inflamación del hígado y la fibrosis tanto in vivo como in vitro. miR-122 se une directamente a la 3’UTR de Sirt1 para suprimir su expresión. Además, la sobreexpresión de Sirt1 revirtió el aumento de la apoptosis celular, el metabolismo de la glucosa y los lípidos, la inflamación del hígado y la fibrosis inducida por los ADEs in vivo e in vitro. Conclusiones: El ADEs miR-122 promueve la progresión de la EHGNA a través de la modulación de la señalización de Sirt1 in vivo e in vitro...(AU)

The anxiolytic drug opipramol inhibits insulin-induced lipogenesis in fat cells and insulin secretion in pancreatic islets

The antidepressant drug opipramol has been reported to exert antilipolytic effect in human adipocytes, suggesting that alongside its neuropharmacological properties, this agent might modulate lipid utilization by peripheral tissues. However, patients treated for depression or anxiety disorders by this tricyclic compound do not exhibit the body weight gain or the glucose tolerance alterations observed with various other antidepressant or antipsychotic agents such as amitriptyline and olanzapine, respectively. To examine whether opipramol reproduces or impairs other actions of insulin, its direct effects on glucose transport, lipogenesis and lipolysis were investigated in adipocytes while its influence on insulin secretion was studied in pancreatic islets. In mouse and rat adipocytes, opipramol did not activate triglyceride breakdown, but partially inhibited the lipolytic action of isoprenaline or forskolin, especially in the 10–100 μM range. At 100 μM, opipramol also inhibited the glucose incorporation into lipids without limiting the glucose transport in mouse adipocytes. In pancreatic islets, opipramol acutely impaired the stimulation of insulin secretion by various activators (high glucose, high potassium, forskolin...). Similar inhibitory effects were observed in mouse and rat pancreatic islets and were reproduced with 100 μM haloperidol, in a manner that was independent from alpha2-adrenoceptor activation but sensitive to Ca2+ release. All these results indicated that the anxiolytic drug opipramol is not only active in central nervous system but also in multiple peripheral tissues and endocrine organs. Due to its capacity to modulate the lipid and carbohydrate metabolisms, opipramol deserves further studies in order to explore its therapeutic potential for the treatment of obese and diabetic states. (AU)

Adipocytes secretome from normal and tumor breast favor breast cancer invasion by metabolic reprogramming

Background Adipose tissue is a major component of breast stroma. This study focused on delineating the effects of adipose stem cells (ASCs) derived from breast of healthy women and cancer patients with normal or tumor breast cells. Methods The ASCs were induced to differentiate into adipocytes, and the subsequent adipocyte conditioned media (ACM) were evaluated for their fatty acid profile, adipokine secretion and influence on proliferation, migration and invasion on tumoral (MCF-7 and SUM159) and normal (HMEC) human breast cell lines. Results An enrichment of arachidonic acid was observed in ACM from tumor tissues. Adipose tissues from tumor free secrete twice as much leptin than those from proximal or distal to the tumor. All ACMs display proliferative activity and favor invasiveness of SUM159 cells compared to MCF-7 and HMEC. All ACMs induced lipid droplets accumulation in MCF-7 cells and increased CD36 expression in tumor cells. Conclusion We conclude that among secreted factors analyzed, only arachidonic acid and leptin levels did discriminate ASCs from tumor-bearing and tumor-free breasts emphasizing the importance that other cell types could contribute to the adipose tissue secretome in a tumor context (AU)

Blockage of NDUFB9-SCD1 pathway inhibits adipogenesis

Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease with an increasing global prevalence associated with tremendous clinical, economic, and health-related quality-of-life burden. Currently, no effective pharmacological therapy is available for NAFLD. Adipogenesis process is accompanied by fat synthesis which may participate in the occurrence and development of NAFLD. Despite intensive investigations, numerous mechanistic aspects of adipogenesis remain unclear and many potential therapeutic targets are yet to be discovered.In this study, the transcriptomics and lipidomics approaches were used to explore the functional genes regulating adipogenesis and the potential mechanism in OP9 cells and adipose-derived stem cells.We find that NADH:ubiquinone oxidoreductase subunit b9 (Ndufb9) is up-regulated in adipogenesis (p < 0.001), and silencing Ndufb9 (83% silencing efficiency) inhibits adipogenesis. The effect of Ndufb9 is mediated through stearoyl-CoA desaturase 1 (Scd1). Aramchol, a SCD1 inhibitor, significantly blocks adipogenesis (markedly TG decrease, p < 0.001).Our study broadens the understanding of the role of Ndufb9 in adipogenesis and provides a new target for the treatment of NAFLD. (AU)

High doses of tyramine stimulate glucose transport in human fat cells

Among the dietary amines present in foods and beverages, tyramine has been widely studied since its excessive ingestion can cause catecholamine release and hypertensive crisis. However, tyramine exerts other actions than depleting nerve endings: it activates subtypes of trace amine associated receptors (TAARs) and is oxidized by monoamine oxidases (MAO). Although we have recently described that tyramine is antilipolytic in human adipocytes, no clear evidence has been reported about its effects on glucose transport in the same cell model, while tyramine mimics various insulin-like effects in rodent fat cells, such as activation of glucose transport, lipogenesis, and adipogenesis. Our aim was therefore to characterize the effects of tyramine on glucose transport in human adipocytes. The uptake of the non-metabolizable analogue 2-deoxyglucose (2-DG) was explored in adipocytes from human subcutaneous abdominal adipose tissue obtained from women undergoing reconstructive surgery. Human insulin used as reference agent multiplied by three times the basal 2-DG uptake. Tyramine was ineffective from 0.01 to 10 µM and stimulatory at 100 µM-1 mM, without reaching the maximal effect of insulin. This partial insulin-like effect was not improved by vanadium and was impaired by MAO-A and MAO-B inhibitors. Contrarily to benzylamine, mainly oxidized by semicarbazide-sensitive amine oxidase (SSAO), tyramine activation of glucose transport was not inhibited by semicarbazide. Tyramine effect was not dependent on the Gi-coupled receptor activation but was impaired by antioxidants and reproduced by hydrogen peroxide. In all, the oxidation of high doses of tyramine, already reported to inhibit lipolysis in human fat cells, also partially mimic another effect of insulin in these cells, the glucose uptake activation. Thus, other MAO substrates are potentially able to modulate carbohydrate metabolism. (AU)

Remodelación autóloga mamaria. Importancia de la transferencia grasa y uso de los colgajos dermograsos locales en las grandes pérdidas ponderales / Autologous breast remodeling. Importance of fat transfer and use of local dermal-fat flaps in the massive weigth loss

INTRODUCCIÓN Y OBJETIVO: El aumento de la cirugía bariátrica como alternativa al tratamiento tanto del síndrome metabólico como de la obesidad y el sobrepeso, conlleva múltiples deformidades corporales, entre las que unas de las más complejas son las alteraciones mamarias. Su tratamiento quirúrgico depende de un diagnóstico y técnica adecuados, capaces de remodelar la estética mamaria. El objetivo de esta investigación es definir la importancia del injerto de grasa como procedimiento previo a la mamoplastia en pacientes que han sufrido grandes pérdidas ponderales. MATERIAL Y MÉTODO: Realizamos un estudio retrospectivo, lineal, en 124 pacientes sometidas a 158 procedimientos quirúrgicos consecutivos entre enero de 2009 y diciembre de 2019, con rango de edad entre 18 y 72 años. Evaluamos los procedimientos para la corrección de las diversas deformidades mamarias tales como, hipotrofia o atrofia mamaria, ptosis, asimetrías, posicionamiento lateralizado del complejo areola pezón, pérdida de la proyección del polo superior, flacidez cutánea asociada a lipodistrofia corporal persistente, cirugías previas de contorno corporal, así como la edad y el índice de masa corporal (IMC). RESULTADOS: El mayor porcentaje de procedimientos correspondió a la triple interposición de colgajos (28%, 44 procedimientos), seguida del injerto de grasa mamaria (27%, 42 procedimientos) y la triple interposición de colgajos con implante de silicona (19%, 30 procedimientos). Se realizó injerto graso mamario en un 40.50% de los procedimientos realizados, con una media de volumen graso infiltrado de 450.60 ml. CONCLUSIONES: Recomendamos la realización de injertos de grasa en todas las pacientes sometidas a cirugía de remodelación mamaria secundaria a pérdida masiva de peso con el fin de recomponer volumétricamente la mama y reconstruir estructuras cutáneas, parenquimatosas y musculares, siendo la transferencia de grasa mamaria la única forma de relleno definitiva del polo superior. Los colgajos locales representan no solo una forma de aumento volumétrico de la mama sino también una posibilidad de mejorar el contorno mamario y el segmento superior del cuerpo

BACKGRAUND AND OBJECTIVE: The increase in bariatric surgery as an alternative to the treatment of both the metabolic syndrome and obesity and overweight leads to multiple bodily deformities, among these one of the most complex are mammary alterations. The surgical treatment of these alterations depends on an adequate diagnosis and a suitable technique able to reshape the mammary aesthetics. The objective of this research is to define the importance of fat grafting as a procedure prior to breast-plasty in patients with post-weight loss. METHODS: A retrospective and linear study was performed in 124 patients, who underwent 158 consecutive procedures between January 2009 and December 2019, age range between 18 and 72 years. The evaluated procedures allowed correction of different breast deformities such as hypotrophy or breast atrophy, ptosis, asymmetries, lateral positioning of the nipple areola complex, loss of the upper pole projection, skin flaccidity associated with persistent body lipodystrophy, previous body contour surgeries, and patient's age and body mass index (BMI). RESULTS: A total of 158 procedures were performed which the highest percentage was of triple flap interposition (28%, 44 procedures), followed by breast fat grafting (27%, 42 procedures) and triple flap interposition with silicone implants (19%, 30 procedures). The fat graft to breast was performed in 40.50% of the total procedures performed, with a mean infiltrated fat volume corresponded to 450.60 ml. CONCLUSIONS: We recommend performing fat grafts in all patients undergoing breast remodeling procedures after massive weight loss in order to volumetrically recompose the breast and rebuild skin, parenchymal and muscular structures, with breast fat transfer being the only way definitive filling of the upper pole. In addition, local flaps represent not only a form of volumetric augmentation of the breast but also a possibility of improving the breast contour and upper body segment

Nevus lipomatoso superficial gigante / Giant Nevus Lipomatosus Cutaneous Superficialis

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Evaluación de cambios histopatológicos secundarios a cirugía bariátrica / Evaluation of histopathological changes secondary to bariatric surgery

Introducción y Objetivo: Los estímulos fisiológicos, como la pérdida masiva de peso, proporcionan adaptaciones celulares en las que se alcanza un nuevo equilibrio que preserva la viabilidad de la célula, lo que se conoce como cambios adaptativos celulares. En nuestro trabajo nos planteamos la siguiente hipótesis: ¿podemos demostrar los cambios adaptativos fisiomorfológicos, histológicos e inmunohistoquímicos celulares sufridos por la piel y la grasa de los pacientes con pérdida masiva de peso? Material y Método: Llevamos a cabo un estudio experimental, descriptivo, prospectivo y comparativo de casos y controles, con una muestra al azar dividida en 2 grupos: A, pacientes postbariátricos y B, pacientes no postbariátricos. Resultados: Las muestras de piel de los pacientes postbariátricos presentaron cambios en el epitelio, colágeno, dermis y adipocitos. Conclusiones: Demostramos la presencia de cambios adaptativos celulares en la piel y la grasa de los pacientes con pérdida masiva de peso, que nos permiten establecer que existe un patrón histológico postbariátrico. Estos datos mejoran nuestro enfoque médico y quirúrgico en la búsqueda de menores complicaciones con mejores resultados en las cirugías de readaptación de contorno corporal a las que pueden someterse dichos pacientes

Background and Objective: The physiological stimuli, such as massive weight loss, provide cellular adaptations in which a new balance that preserves cell viability is reached, what is known as cellular adaptive changes. Our hypothesis in this study was: can we show fisiomorfológic cellular, histological and immunohistochemical adaptive changes suffered by the skin and fat of patients with massive weight loss? Methods: An experimental, descriptive, prospective and comparative case-control study was conducted on a random sample divided into 2 groups: A, postbariátric patients and B, no postbariatric patients. Results: Skin samples from postbariátric patients showed changes in the epithelium, collagen, dermis and fat cells. Conclusions: Cellular adaptive changes in the skin and fat of patients with massive weight loss are shown. These data improve our medical and surgical approach in finding minor complications with better aesthetic results when these patients undergo a body contouring surgery

Lipid metabolism in adipose tissue and liver from diet-induced obese rats: a comparison between Wistar and Sprague-Dawley strains

Some researchers have proposed important variations in adipose tissue among different strains of rats and mice in response to a high-caloric (hc) diet, but data concerning the mechanisms underlying these differences are scarce. The aim of the present research was to characterize different aspects of triacylglycerol (TG) metabolism and clock genes between Sprague-Dawley and Wistar rats. For this purpose, 16 male Sprague-Dawley and 16 male Wistar rats were divided into four experimental groups (n = 8) and fed either a normal-caloric (nc) diet or a hc diet for 6 weeks. After sacrifice, liver and epididymal, perirenal, mesenteric, and subcutaneous adipose tissue depots were dissected, weighed and immediately frozen. Liver TG content was quantified, RNA extracted for gene expression analysis and fatty acid synthase enzyme activity measured. Two-way ANOVA and Student’s t test were used to perform the statistical analyses. Under hc feeding conditions, Wistar rats were more prone to fat accumulation in adipose tissue, especially in the epididymal fat depot, due to their increased lipogenesis and fatty acid uptake. By contrast, both strains of rats showed similarly fatty livers after hc feeding. Peripheral clock machinery seems to be a potential explanatory mechanism for Wistar and Sprague-Dawley strain differences. In conclusion, Wistar strain seems to be the best choice as animal model in dietary-induced obesity studies

Association of a cholesteryl ester transfer protein variant (rs1800777) with fat mass, HDL cholesterol levels, and metabolic syndrome / Asociación de la variante (rs1800777) de proteína de transferencia de ésteres de colesterol con masa grasa, niveles de colesterol HDL y síndrome metabólico

Background: There is little evidence of the association between CETP SNPs and obesity and/or related metabolic parameters. Objective: To analyze the association of the polymorphism rs1800777 of the CETP gene with anthropometric parameters, lipid profile, metabolic syndrome and its components, and adipokine levels in obese subjects without type 2 diabetes mellitus or hypertension. Design: A population of 1005 obese subjects was analyzed. Electrical bioimpedance was performed, and blood pressure, presence of metabolic syndrome, dietary intake, physical activity, and biochemical tests were recorded. Results: Nine hundred and sixty eight patients (96.3%) had the GG genotype, 37 patients the GA genotype (3.7%) (no AA genotype was detected). Fat mass (delta: 4.4±1.1kg; p=0.04), waist circumference (delta: 5.6±2.1cm; p=0.02), and waist to hip ratio (delta: 0.04±0.01cm; p=0.01) were higher in A allele carriers than in non-A allele carriers. HDL cholesterol levels were lower in A allele carriers than in non-A allele carriers (delta: 4.2±1.0mg/dL; p=0.04). In the logistic regression analysis, the GA genotype was associated to an increased risk of central obesity (OR 7.55, 95% CI 1.10-55.70, p=0.02) and low HDL cholesterol levels (OR 2.46, 95% CI 1.23-4.91, p=0.014). Conclusion: The CETP variant at position +82 is associated to lower HDL cholesterol levels, increased fat mass, and central obesity in obese subjects. These results may suggest a potential role of this variant gene in pathophysiology of adipose tissue

Antecedentes: Existen pocas evidencias en relación a la asociación entre los SNP de CETP y la presencia de obesidad y/o parámetros metabólicos relacionados. Objetivo: Examinar la asociación del polimorfismo (rs1800777) del gen CETP con parámetros antropométricos, perfil lipídico, presencia de síndrome metabólico y sus diferentes componentes y los niveles de adipocitoquinas en sujetos con obesidad sin diabetes mellitus ni hipertensión. Diseño: Se analizó una población de 1.005 sujetos con obesidad. Se registró una bioimpedancia, presión arterial, presencia de síndrome metabólico, ingesta dietética, ejercicio físico y parámetros bioquímicos. Resultados: Novecientos sesenta y ocho pacientes (96,3%) tuvieron el genotipo GG y 37 pacientes presentaron el genotipo GA (3,7%) (no se detectó genotipo AA). La masa grasa (delta: 4,4±1,1kg; p=0,04), circunferencia de la cintura (delta: 5,6±2,1cm; p=0,02), relación cintura-cadera (delta: 0,04±0,01cm; p=0,01) fueron mayores en los portadores del alelo A. El colesterol HDL fue menor en los portadores del alelo A (delta: 4,2±1,0mg/dl; p=0,04). En el análisis de regresión logística la presencia del alelo A se asoció con un mayor riesgo de obesidad central (OR: 7,55; IC 95%: 1,10-55,70; p=0,02) y un mayor riesgo de colesterol HDL bajo (OR: 2,46; IC 95%: 1,23-4,91; p=0,014). Conclusión: La variante CETP en la posición +82 se asocia a unos niveles más bajos de colesterol HDL, a un mayor porcentaje de masa grasa y obesidad central en personas con obesidad. Estos resultados podrían sugerir un posible papel de esta variante en la fisiopatología del tejido adiposo

Cell source, differentiation, functional stimulation, and potential application of human thermogenic adipocytes in vitro

Recent investigations have showed that the functional thermogenic adipocytes are present in both infants and adult humans. Accumulating evidence suggests that the coexistence of classical and inducible brown (brite) adipocytes in humans at adulthood and these adipocytes function to generate heat from energy resulting in reducing body fat and improving glucose metabolism. Human thermogenic adipocytes can be differentiated in vitro from stem cells, cell lines, or adipose stromal vascular fraction. Pre-activated human brite adipocytes in vitro can maintain their thermogenic function in normal or obese immunodeficient mice; therefore, they improve glucose homeostasis and reduce fat mass in obese animals. These key findings have opened a new door to use in vitro thermogenic adipocytes as a cell therapy to prevent obesity and related disorders. Thus, this paper intends to highlight our knowledge in aspects of in vitro human brite/brown adipocytes for the further studies

Rol de los receptores de adenosina en la interacción adipocito-macrófago durante la obesidad / Role of adenosine receptors in the adipocyte-macrophage interaction during obesity

La inflamación generada en el tejido adiposo o lipoinflamación, puede contribuir al desarrollo de la resistencia a la insulina. Los mecanismos asociados a la lipoinflamación están relacionados con la función de los adipocitos y los macrófagos presentes en el tejido adiposo. En este contexto, el nivel del nucleósido adenosina está aumentado en individuos con obesidad. Las causas o consecuencias de este aumento no se conocen. Aunque, adenosina al activar a sus receptores (A1, A2A, A2B y A3) es capaz de modular diferencialmente la función de adipocitos y macrófagos, con el fin de evitar la reducción de la sensibilidad a la insulina y generar un estado antiinflamatorio en el individuo con obesidad. En esta revisión proponemos que adenosina podría ser un elemento clave en el desarrollo de nuevas estrategias para el control de la lipoinflamación y homeostasis metabólica a través de la regulación del diálogo adipocito-macrófago (AU)

Lipoinflamation is the inflammation generated in the adipose tissue. It can contribute to the development of insulin resistance. The lipoinflammation-associated mechanisms are related to the function of adipocytes and macrophages present in the adipose tissue. In this regard, the level of nucleoside adenosine is increased in individuals with obesity. Causes or consequences of this increase are unknown. Although, adenosine activating its receptors (A1, A2A, A2B and A3) is able to differentially modulate the function of adipocytes and macrophages, in order to avoid the reduction of insulin sensitivity and generate an anti-inflammatory state in subject with obesity. In this review we propose that adenosine could be a key element in the development of new strategies for limit lipoinflammation and regulate metabolic homeostasis through modulation of adipocyte-macrophage dialogue (AU)

Lipoatrofia semicircular: 3 casos clínicos / Semicircular lipoatrophy: three clinical cases

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Acumulación de adipocitos en el cuerpo cavernoso: primera evidencia clínica e implicaciones fisiopatológicas en la disfunción eréctil / Adipocyte accumulation in corpus cavernosum: first clinical evidence and pathophysiological implications in erectile dysfunction

Objetivo: Modelos animales han demostrado que existe una asociación entre disfunción eréctil y acumulación de grasa bajo la albugínea del pene, pudiendo provocar fuga venosa y pérdida de rigidez del pene. En este estudio se llevó a cabo una comparación de la histología de los cuerpos cavernosos bajo la albugínea de pacientes con disfunción eréctil refractarios a tratamiento médico sometidos a implante de prótesis de pene, y pacientes con enfermedad de Peyronie, sin disfunción eréctil, sometidos a corporoplastia. Materiales y métodos: Se incluyeron 17 pacientes con disfunción eréctil y 14 pacientes potentes con enfermedad de Peyronie. Se recolectaron muestras de tejido cavernoso bajo la túnica albugínea en cada cirugía, las cuales fueron analizadas por un uropatólogo en búsqueda de adipocitos subalbugíneos. Se llevó a cabo un análisis bivariado para comparar características de ambos grupos. Se calcularon las odds ratio con un modelo multivariado de regresión logística. Un valor de p < 0,05 fue considerado significativo. Resultados: Once pacientes (11/17) en el grupo de disfunción eréctil presentaron adipocitos en la histología, mientras solo un paciente (1/14) lo presentó en el grupo control (p < 0,05). El análisis multivariado mostró una odds ratio de 40,72; IC 95%: 2,28-727,29 (p = 0,012). Conclusiones: Alteraciones en los andrógenos provocan cambios estructurales en el pene, llevando a apoptosis y desdiferenciación de músculo trabecular hacia adipocitos. Este es el primer estudio prospectivo en humanos que muestra una asociación entre grasa subalbugínea y disfunción eréctil. La fuga venosa secundaria a este fenómeno podría influir en la disfunción eréctil, especialmente en pacientes que no responden a tratamiento médico

Objectives: Animal models have shown that erectile dysfunction is associated with adipocyte accumulation under tunica albugínea, which could be involved in venous leakage and loss of penile rigidity. In the current sudy, we compared the histology of the penile sub-albuginean region of drug-refractory erectile dysfunction patients undergoing penile prosthesis implantation with potent patients with Peyronie's disease undergoing curvature correction procedures. Materials and methods. Seventeen refractory erectile dysfunction patients and fourteen potent patients with Peyronie's disease were recruited. Sub-albuginean tissue samples were taken in each surgery. An expert uropathologist analysed each section. A bivariate analysis was performed. Multivariate logistic regression was used to calculate adjusted odds ratios; P value <.05 was considered significant. Results: Eleven patients (11/17) in the case group presented cavernous fat cell accumulation, while only one patient (1/14) in the control group presented this finding (P < .05). Adjusted odds ratio for erectile dysfunction was 40.72; 95% CI 2.28-727.29 (P = .012). Conclusions: Different studies have shown that androgen disruption could be involved in penile structural changes, leading to trabecular smooth muscle apoptosis and trans or de-differentiation into adipocytes. This is the first prospective study in humans to report an association between erectile dysfunction and sub-albuginean adipocyte accumulation. Venous leakage secondary to this phenomenon could be a factor in the pathophysiology of erectile dysfunction, especially in patients that do not respond to medical therapy

Aplicaciones clínicas de células madres derivadas de tejido adiposo y aspectos relacionados con buenas prácticas de manufactura / Clinical applications of adipose-derived stem cells and aspects related with good manufacturing practices

En la actualidad la terapia celular, a través de las aplicaciones clínicas de las células madres (stem cell, SC), ha adquirido importancia como tratamiento frente a enfermedades que involucran la reparación de tejidos u órganos, frente a las cuales el organismo no es capaz de responder adecuadamente. Un campo de reciente interés se centra en el uso de células madres derivadas de adipocitos (adipose-derived stem cells, ASCs), que presentan ventajas en comparación a las células madres mesenquimales derivadas de médula ósea (mesenchymal stem cells derived from bone marrow, MSC-BM), las que han sido ampliamente investigadas. Los múltiples estudios enfocados en las aplicaciones clínicas de este tipo celular han sido muy prometedores y satisfactorios, lo que ha permitido que recientemente hayan sido aprobadas por la Agencia Europea del Medicamento (EMA) para el tratamiento de fístulas complejas en enfermedad de Crohn. Como consecuencia de lo anterior, al igual que cualquier medicamento de uso humano, requieren de un sistema de normas que regule su producción, como son las Buenas Prácticas de Manufactura (BPM), cuyo objetivo es asegurar la eficacia y seguridad para los pacientes. En esta revisión se abordan aspectos relevantes en relación a las ventajas, aplicaciones clínicas y normas que rigen la producción de ASCs (AU)

Currently, cell therapy through the clinical use of stem cells (SC) has acquired relevance as a treatment for diseases involving tissue or organ repair, in which the organism is not able to properly respond. An area of recent interest is focused on the use of adipose-derived stem cells (ASCs) that exhibit advantages in comparison to the bone marrow-derived mesenchymal stem cells (MSC-BM), which have been widely investigated. Multiple studies focused on the clinical applications of this type of cells have been promising and satisfying, which allowed their recent approval by the European Medicines Agency (EMA) for the treatment of complex fistulas in Crohn´s disease. In consequence, as for any human use medicine, they require a system of standards that regulate their production, as the good manufacturing practices (GMP), whose aim is to assure the efficacy and safety for the patients. This review addresses relevant aspects related to the advantages, clinical applications and standards that regulate ASCs production (AU)

Melatonin attenuated adipogenesis through reduction of the CCAAT/enhancer binding protein beta by regulating the glycogen synthase 3 beta in human mesenchymal stem cells

Adipogenic differentiation is characterized by an increase in two major transcription factors: peroxisome proliferator-activated receptor gamma (PPARγ) and the CCAAT/enhancer binding protein alpha (C/EBPα). These two signals are influenced by C/EBPβ and C/EBPδ and cross-regulate each other’s expression during the initial stages of adipogenesis. Melatonin has been known to act as not only a direct scavenger of free radicals but also an inhibitor of glycogen synthase kinase 3β (GSK-3β). Here, we report that melatonin inhibits the adipogenic differentiation of human mesenchymal stem cells (hMSCs) which is due to the regulations of C/EBPβ in the early stage of adipogenic differentiation. Melatonin reduced the lipid accumulation, adiponectin, and lipoprotein lipase (LPL) during the adipogenic differentiation of hMSCs. Since C/EBPβ has been associated with the activation of PPARγ and the consensus site of ERK/GSK-3β, PPARγ and β-catenin were detected by immunofluorescence staining after pretreatment of melatonin. Melatonin blocked the activation of PPARγ which induced the degradation of β-catenin. Melatonin also decreased the levels of cyclic adenosine-3,5-monophosphate (cAMP) and reactive oxygen species (ROS). The cAMP triggered the activity of C/EBPβ which is a critical inducer of PPARγ and C/EBPα activation in the early stage of adipogenic differentiation, and this is further affected by ROS production. The adipogenic marker proteins such as PPARγ, C/EBPα, C/EBPβ, and pERK were also decreased by melatonin. In summary, melatonin inhibited the cAMP synthesis through ROS reduction and the phosphorylation of the ERK/GSK-3β site which is known to be responsible for C/EBPβ activation for adipogenic differentiation in hMSCs (AU)

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Lipomatosis cardiaca masiva, hallazgo en la autopsia de un paciente con muerte súbita / Massive cardiac lipomatosis, an autopsy finding in a patient with sudden death

La sustitución grasa de las células miocárdicas es un proceso degenerativo que afecta en mayor medida al ventrículo derecho y se encuentra en el 50% de las personas ancianas. El problema se origina cuando esta degeneración se produce en grado masivo, planteando la necesidad de realizar el diagnóstico diferencial con otras enfermedades. Se presenta el caso de un paciente que falleció de forma súbita y en su autopsia se encontró esta dolencia como única explicación del desenlace (AU)

The fat replacement of myocardial cells is a degenerative process that usually affects the right ventricle and is found in 50% of the elderly. The problem arises when this degeneration occurs to a massive degree, a differential diagnosis with other pathologies being necessary. We present the case of a patient who died suddenly and a massive cardiac lipomatosis was found on autopsy, as the only explanation of the outcome (AU)