Treadmill running alleviates adipose tissue browning and lipolysis in rats with heart failure

This study observed the effects of treadmill running on adipose tissue browning and lipolysis in rats with induced heart failure and elucidated the possible mechanism. Rats underwent abdominal aortic constriction as a model of heart failure. Cardiac function was detected by echocardiography. We detected serum levels of norepinephrine and interleukin 6, cardiac atrial natriuretic peptide and brain natriuretic peptide and marker genes of browning, white adipose tissue (WAT), and lipolysis in adipose tissue. Rats with heart failure showed typical symptoms such as increased heart weight and mRNA levels of atrial natriuretic peptide and brain natriuretic peptide and decreased left ventricular ejection fraction. Exercise partially improved left ventricular diastolic function and significantly decreased atrial natriuretic peptide expression. Rats with heart failure showed significantly reduced body weight and ratios of muscle and fat weight to body weight. Exercise significantly increased body weight and the ratio of muscle weight to body weight. Heart failure stimulated the expression of proliferator-activated receptor-gamma coactivator-1-alpha and uncoupling protein 1 in epididymal WAT, inguinal WAT, and brown adipose tissue but decreased that of adiponectin and leptin in inguinal WAT. Lipolysis, characterized by high adipose triglyceride lipase and hormone-sensitive lipase expression, was activated in all adipose tissues. Exercise reduced browning and lipolysis in adipose tissues. Rats with heart failure had abnormally high levels of serum norepinephrine and interleukin 6, which could be suppressed by exercise. Exercise may improve cardiac cachexia and inhibit the browning and lipolysis of adipose tissue by downregulating sympathetic nervous system activity and inflammation. (AU)

Adiponectin overexpression in C2C12 myocytes increases lipid oxidation and myofiber transition

Metabolic syndrome and obesity have detrimental effects on the metabolic function of the skeletal muscle. Mounting evidence indicates that patients with those conditions may present an increased ratio of glycolytic to oxidative fibers associated with a decrease in oxidative capacity. In this regard, adiponectin, a hormone mainly secreted by adipocytes that regulates glucose and lipid metabolism, has emerged as a myokine that could play an important role in this process. We aimed to investigate whether adiponectin overexpression in skeletal muscle might be a local protective mechanism, favoring fatty acid utilization. To that end, we generated an in vitro model of myocytes with upregulated endogenous adiponectin using a lentiviral carrier. We demonstrated that the adiponectin-transduced myocytes were able to produce and secrete fully functional adiponectin complexes. Adiponectin overexpression remarkably upregulated the mRNA level of myogenic regulatory factors as well as genes implicated in lipolysis (HSL, ATGL) and cellular and mitochondrial fatty acid transport (LPL, CD36, CPT1B). This was accompanied by increased isoproterenol-induced lipolysis and β-oxidation and reduced lipogenesis, whereas insulin-stimulated glucose uptake was unaltered in transduced myocytes. Lastly, the relative expression of the more glycolytic myofibers (MyHC IIb) compared to the more oxidative ones (MyHC I) was notably reduced. Our results showed that the released adiponectin acted in an autocrine/paracrine manner, increasing lipid oxidation in myocytes and leading to a transition of myofibers from the glycolytic to the oxidative type. In conclusion, muscle adiponectin overexpression might be a way to relieve muscle diseases caused by oxidative muscle fiber deficiency. (AU)

Efectos del ultrasonido externo sobre el panículo adiposo. Modelo porcino experimental / Effects of external ultrasound on the adipose panicle. Experimental pig model

INTRODUCCIÓN Y OBJETIVO: El ultrasonido (US) externo o percutáneo, ampliamente utilizado, ocasiona diferentes efectos histológicos dependiendo de la frecuencia, intensidad, amplitud de onda, tiempo de aplicación y de los tejidos a través de los cuales curse. Se ha utilizado con diferentes propósitos, entre otros para facilitar la liposucción y mejorar sus resultados; sin embargo, hasta donde hemos podido revisar, no hay reportes que relacionen las frecuencias del US percutáneo y el lapso de su aplicación con los cambios descritos en el panículo adiposo. El objetivo del presente estudio es establecer parámetros de frecuencia y tiempos de aplicación del US externo para uniformar criterios en base al análisis histológico de los cambios que ocasiona al panículo adiposo y a los adipocitos. MATERIAL Y MÉTODO: Estudio descriptivo, comparativo, abierto, experimental, prospectivo y longitudinal, en 59 fragmentos de tejido adiposo tomados de cerdos adultos. Cinco fragmentos fueron preservados como control; los 54 restantes fueron sometidos a US directo sobre cada fragmento, con diferentes parámetros de tiempo (5, 10 y 15 minutos) y diferentes frecuencias (baja- 1.1 Hz, media- 2.4 Hz y alta- 3.9 Hz). Fueron procesados en 2 formas (parafina y congelación) y teñidos con 2 técnicas (hematoxilina/eosina y rojo oleoso). En cada laminilla se observaron 10 campos. RESULTADOS: En los fragmentos de control observamos tejido adiposo maduro normal. En los sometidos a US, dependiendo de la frecuencia y el tiempo aplicado, observamos edema intersticial, desarreglo de su arquitectura, lisis de la membrana de los adipocitos e infiltrado inflamatorio, en diversos porcentajes, que calificamos en grados. Así en los fragmentos expuestos durante 5 minutos a frecuencia media hubo lisis leve (10%), igual que en los expuestos 10 minutos a frecuencia baja. En los expuestos 10 minutos a frecuencia media la lisis fue de leve a moderada (10-20%), semejante a la observada con frecuencia baja durante 15 minutos. Aplicando US durante 15 minutos con frecuencia baja la respuesta fue de leve a moderada (10-20%), con frecuencia media fue de moderada a severa (20-30%) y con frecuencia alta fue francamente severa (30%). CONCLUSIONES: La aplicación de US externo ocasiona lisis de los adipocitos y evidentes desarreglos en la arquitectura del tejido adiposo. Aplicarlo con frecuencias menores requiere periodos más largos para lograr los mismos efectos. Con frecuencias mayores se logran los cambios en menos tiempo. El empleo de frecuencias de 2.4 a 3.9 Hz ocasiona cambios evidentes, con amplio margen de seguridad

BACKGROUND AND OBJECTIVE: External or percutaneous ultrasound (US) widely used, causes different histological effects depending on the frequency, intensity, wave amplitude, application time and the tissues through which it passes. It has been used for different purposes, among others, to facilitate liposuction and improve its results; however, as far as we have been able to review, there are no reports that relate the frequencies of the percutaneous US and the period of its application with the changes described in the adipose tissue. Our aim is to establish frequency parameters and application times of the external US to standardize criteria, based on the histological analysis of the changes it causes to the adipose panniculus and to the adipocytes. METHODS: A descriptive, comparative, open, experimental, prospective and longitudinal study was carried out in 59 fragments of adipose tissue taken from adult pigs. Fifty-four were subjected to US applied directly to each fragment, with different time parameters (5, 10 and 15 minutes) and different frequencies (low-1.1 Hz, medium-2.4 Hz and high-3.9 Hz). Five fragments were preserved as a control. Processed in 2 ways (paraffin and freezing) and stained with 2 techniques (hematoxylin/eosin and oil red). In each lamella 10 fields were observed. RESULTS: Normal mature adipose tissue was observed in the control fragments. In those undergoing US, depending on the frequency and time applied, interstitial edema, disordered architecture, presence of inflammatory infiltrate and lysis of adipocyte membranes were observed, in various percentages that we qualified in degrees. Thus, in the fragments exposed for 5 minutes at medium frequency, mild lysis was observed (10%), In those exposed for 10 minutes at medium frequency, lysis was mild to moderate ( 10-20%), similar to that observed with low frequency for 15 minutes. Applying US for 15 minutes with low frequency, the response was mild to moderate (10-20%) with medium frequency of moderate to severe (20-30%) and with high frequency it was frankly severe (30%). CONCLUSIONS: The application of external US causes lysis of the adipocytes and evident disorders in the adipose tissue architecture. Applying it with lower frequencies requires longer periods to achieve the same effects. With higher frequencies the same changes are achieved in less time. The use of frequencies from 2.4 to 3.9 Hz causes obvious changes, with a wide margin of safety

miR-128-3p regulates 3T3-L1 adipogenesis and lipolysis by targeting Pparg and Sertad2

Differentiation of adipocytes and their aggregation to adipose tissue are critical for mammalian growth and development. MicroRNAs (miRNAs) are a class of endogenous small non-coding RNAs that play important roles in adipogenesis and lipid metabolism. miR-128-3p may contribute to adipose tissue development according to the previous studies. However, the role of miR-128-3p in the process of preadipocyte differentiation and lipid metabolism is not yet understood. The purpose of this research was to investigate the biological function and molecular mechanism of miR-128-3p in 3T3-L1 cells. In the present study, we found that miR-128-3p was downregulated during the process of 3T3-L1 preadipocyte differentiation. Overexpression of miR-128-3p obstructed the expressions of adipogenic marker genes as well as the lipid droplets accumulation and triglyceride content, suggesting the importance of miR-128-3p for adipogenesis. Moreover, miR-128-3p could lead to the retardation of cell proliferation in 3T3-L1 preadipocytes. Further evidences showed that, as a negative regulator of adipogenesis, miR-128-3p could directly target peroxisome proliferator-activated receptor γ (Pparg) which resulted in the suppression of 3T3-L1 preadipocyte differentiation, and miR-128-3p could also bind with SERTA domain containing 2 (Sertad2) which drove triglyceride hydrolysis and lipolysis. In addition, inhibition of Sertad2 with siRNA displayed the same effects as overexpression of miR-128-3p. Our research demonstrated that miR-128-3p impeded 3T3-L1 adipogenesis by targeting Pparg and Sertad2, resulting in the obstruction of preadipocyte differentiation and promotion of lipolysis. Taken together, this study offers profound insight into the mechanism of miRNA-mediated adipogenesis and lipid metabolism

Zinc alpha-2 glycoprotein is overproduced in Cushing's syndrome / Aumento de la glucoproteína zinc alfa-2 en el síndrome de Cushing

Introduction: Cushing syndrome (CS), an endogenous hypercortisolemic condition with increased cardiometabolic morbidity, leads to development of abdominal obesity, insulin resistance, diabetes and proatherogenic dyslipidemia. Zinc alpha-2 glycoprotein (ZAG) is a recently characterized lipolytic adipokine implicated in regulation of adipose tissue metabolism and fat distribution. In vitro and animal studies suggest that glucocorticoids interact with ZAG secretion and action. To assess the relationship between ZAG and glucocorticoids in a human model of hypercortisolism, circulating ZAG levels were tested in patients with CS and its counterpart controls. Methods: An observational, cross-sectional study on 39 women, 13 with active CS and 26 controls matched by age and body mass index. Plasma ZAG levels (μg/ml) were measured by ELISA and correlated with hypercortisolism, metabolic, and phenotypic parameters. Results: Plasma ZAG levels were significantly higher in patients with CS compared to controls (64.3±16.6 vs. 44.0±16.1, p=0.002). In a univariate analysis, ZAG levels positively correlated to 24-h urinary free cortisol (p=0.001), body mass index (p=0.02), non-esterified fatty acids (p=0.05), glucose (p=0.003), LDL-C (p=0.028), and type 2 diabetes mellitus (p=0.016), and were inversely related to total adiponectin levels (p=0.035). In a multivariate analysis, after adjusting for CS, ZAG levels only correlated with body mass index (p=0.012), type 2 diabetes mellitus (p=0.004), and glucose (p<0.001). Conclusion: This study provides initial evidence that plasma ZAG levels are higher in patients with CS as compared to controls. The close relationship of ZAG with metabolic and phenotypic changes in CS suggests that ZAG may play a significant role in adipose tissue changes in hypercortisolism (AU)

Introducción: El síndrome de Cushing (SC) es un estado de hipercortisolismo endógeno en el que se observa un incremento del riesgo cardiovascular asociado al desarrollo de obesidad abdominal, insulinorresistencia, diabetes y dislipidemia aterogénica. La zinc alfa-2 glucoproteína (ZAG) es una adipocina lipolítica recientemente caracterizada que está implicada en la regulación del metabolismo del tejido adiposo y la distribución de la grasa. Estudios in vitro y en animales indican que los glucocorticoides interaccionan con la secreción y acción de ZAG. Para evaluar la relación entre ZAG y los glucocorticoides en un modelo humano de hipercortisolismo, se analizaron los niveles circulantes de ZAG en pacientes con SC y sus correspondientes controles. Métodos: Estudio observacional en 39 mujeres, 13 con SC activo y 26 controles pareadas por edad e índice de masa corporal. Los niveles plasmáticos de ZAG (μg/ml) se determinaron mediante ELISA y se correlacionaron con los parámetros de hipercortisolismo, metabólicos y fenotípicos. Resultados: Las concentraciones plasmáticas de ZAG fueron significativamente más elevadas en los pacientes con SC (64,3±16,6 vs. 44±16,1; p=0,002). En el análisis univariante los niveles de ZAG se correlacionaron positivamente con cortisol libre urinario (p=0,001), índice de masa corporal (p=0,02), ácidos grasos no esterificados (p=0,05), glucosa (p=0,003), c-LDL (p=0,028) y diabetes mellitus (p=0,016) e inversamente con adiponectina total (p=0,035). En el análisis multivariante, después de ajustar por el SC, los niveles de ZAG solo se correlacionaron con el índice de masa corporal (p=0,012), la diabetes mellitus tipo 2 (p=0,004) y la glucosa (p<0,001). Conclusión: Nuestro estudio proporciona la primera evidencia de las concentraciones plasmáticas de ZAG en el SC. Los pacientes con SC presentan concentraciones más elevadas de ZAG que los controles. La estrecha relación de ZAG con las alteraciones metabólicas y fenotípicas del SC indica que ZAG podría desempeñar un papel importante en las alteraciones del tejido adiposo en el hipercortisolismo (AU)

Tratamiento de la hiperglucemia en pacientes con ictus agudo / Treatment of hyperglycaemia in patients with acute stroke

La proporción de pacientes diabéticos hospitalizados por ictus ha ido aumentando en los últimos años, alcanzando en la actualidad casi un tercio de todos los ictus. Además, prácticamente la mitad de los enfermos con ictus agudo pueden presentar hiperglucemia en las primeras horas del evento. A pesar de que la hiperglucemia en la fase aguda del ictus se asocia a un peor pronóstico, su tratamiento es en la actualidad motivo de controversia. No existen evidencias de que la administración de insulina por vía intravenosa en estos pacientes proporcione beneficios en la evolución del ictus. Nuevos estudios en desarrollo, como el estudio Stroke Hyperglycemia Insulin Network Effort (SHINE), posiblemente contribuyan a aclarar el papel del control intensivo de la glucemia durante la fase aguda del ictus. Finalmente, los pacientes que han presentado un ictus deberían ser sometidos a un cribado de diabetes (AU)

The proportion of diabetic patients who are hospitalised for stroke has been increasing in recent years, currently reaching almost a third of all cases of stroke. In addition, about half of patients with acute stroke present hyperglycaemia in the first hours of the stroke. Although hyperglycaemia in the acute phase of stroke is associated with a poor prognosis, its treatment is currently a topic of debate. There is no evidence that the adminstration of intravenous insulin to these patients offers benefits in terms of the evolution of the stroke. New studies in development, such as the SHINE study (Stroke Hyperglycemia Insulin Network Effort), may contribute to clarifying the role of intensive control of glycaemia during the acute phase of the stroke (AU)

Effects of treadmill running and rutin on lipolytic signaling pathways and TRPV4 protein expression in the adipose tissue of diet-induced obese mice

To explore the effects of rutin and exercise on high-fat diet (HFD)-induced disrupted lipolytic signaling, adenosine 5Œ-monophosphate (AMP)-activated protein kinase (AMPK) signaling, transient receptor potential cation channel subfamily V member 4 (TRPV4) and its associated protein expression, and whether depot-specific effects existed. C57BL/6J mice were randomized into five groups: chow group, HFD, HFD plus rutin intervention group (HR), HFD combined with treadmill running group (HE), and HFD combined with treadmill running and rutin intervention group (HRE). At the end of the 16-week intervention, lipolytic markers, AMPK signaling pathways, TRPV4, and peroxisome proliferator-activated receptor gamma coactivator 1Alpha + Beta (PGC-1Alpha + Beta) from adipose tissue were measured by western blotting. In epididymal adipose tissue, HFD resulted in significant reduction in the phosphorylation of hormone sensitive lipase at serine660 (p-HSL660), perilipin A, phosphoenolpyruvate carboxykinase (PEPCK), p-AMPK, and p-acetyl-CoA carboxylase (ACC) protein expression. Exercise intervention and exercise plus rutin completely restored p-HSL660, perilipin A, PEPCK, p-AMPK, and p-ACC protein expression to normal level. HFD and HR groups have reduced expression of PGC-1Alpha + Beta, exercise, and exercise plus rutin completely restored PGC-1Alpha + Beta expression to normal level. In subcutaneous adipose tissue, HFD elevated TRPV4, exercise, and exercise plus rutin completely reduced TRPV4 to normal level. HR, HE, and HRE group have increased PGC-1Alpha + Beta. In conclusion, depot-specific effects existed in regards to how rutin and exercise affect lipolytic signaling and p-AMPK, as well as TRPV4 and PGC-1Alpha + Beta expression

Endurance training in fasting conditions: biological adaptations and body weight management / Entrenamiento aeróbico en ayunas: adaptaciones biológicas y efectos en el control de peso

Introduction: in the majority of sports the athlete is required to achieve optimal conditions both at a muscular and metabolic level as well as in body composition, increasing the lean body mass and maintaining a low body fat mass. In this context, different training protocols have been proposed in order to reduce body fat content, by maximizing fat use instead of glycogen. Objective: to verify if the training while fasting favours the use of fatty acids due to the low glycogen levels, allowing an improvement in the performance ant the control of body weight. Results: protocols have been published, differing in time periods and exercise intensity. In addition, several markers ranging from gene expression analysis to determination of circulating parameters have been assessed in order to interpret the results. Discusion: at low intensities of endurance-based exercises, adipose tissue lipolysis and muscle fat oxidation rate seem to be higher in fasting than in fed state. On the other hand, glucose metabolism is adapted in order to save glycogen stores, possibly through gluconeogenesis activation. Finally, it has been observed that protein degradation is mainly downregulated. Only one study analyses changes in body composition after fasting during long periods, thus further work is necessary to demonstrate that this is the best method to control body fat (AU)

Introducción: en la mayoría de las disciplinas deportivas, el deportista debe conseguir unas óptimas condiciones a nivel muscular y metabólico, así como de composición corporal, manteniendo un bajo porcentaje de grasa corporal. En este contexto se han propuesto diferentes protocolos de entrenamiento con el fin de reducir el porcentaje de grasa corporal incidiendo en un aumento de la utilización de las grasas en detrimento del glucógeno. Objetivo: comprobar si el entrenamiento en ayunas favorece el uso de ácidos grasos debido a los bajos niveles de glucógeno, permitiendo mejoras en el rendimiento y en el control del peso a partir de los estudios publicados. Resultados: los protocolos publicados difieren tanto en el periodo de trabajo como en la intensidad del ejercicio, así como respecto al análisis de una gran variedad de marcadores, desde la expresión de genes hasta parámetros circulantes. Discusión: a bajas intensidades de ejercicio aeróbico, los niveles de lipólisis y oxidación de grasas son mayores en el ejercicio en ayunas. Por otro lado, el metabolismo de la glucosa en condiciones de ayuno se adapta en relación al ahorro de las reservas de glucógeno. Finalmente, en condiciones de ayuno, la degradación de proteínas musculares se ve disminuida. Actualmente solo un estudio analiza los cambios en la composición corporal tras un protocolo de larga duración de ejercicio y ayuno, por lo que es necesario realizar más estudios con el fin de demostrar que se trata de una estrategia válida para el control del peso corporal (AU)

Nuevas tecnologías en cirugía plástica-estética. Presentación / New technologies in Plastic-Aesthetic Surgery. Presentation

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The postprandial situation as a pro-inflammatory condition / La situación posprandial como condición proinflamatoria

Postprandial lipemia has been associated with cardiovascular disease. The current pathophysiological concept is that postprandial remnant lipoproteins migrate into the subendothelial space and that remnants activate circulating leukocytes and endothelial cells. Activated monocytes adhere to endothelial adhesion molecules, facilitating subendothelial migration of monocytes. These cells differentiate into macrophages, with the risk of foam cell formation, due to uptake of remnants and modified lipoproteins. Evidence is emerging that specific interventions may reduce the atherogenic postprandial inflammation. Fruits rich in polyphenols, virgin olive oil, carotenoids and exercise have recently been found to reduce postprandial inflammation. Pharmaceutical interventions with fibrates or statins not only improve the overall lipid profile, but reduce postprandial inflammation as well. This review will deal with the current concept of postprandial inflammation in relation to the development of atherosclerosis and potential interventions to reduce postprandial inflammation

La lipidemia posprandial está relacionada con la enfermedad cardiovascular. El concepto patofisiológico actual es que las partículas remanentes traspasan el endotelio, activan los leucocitos y las células endoteliales. Los monocitos activados se adhieren a la paredendotelial por mediación de moléculas de adhesión, facilitando así la migración de los monocitos al espacio subendotelial. Estas células se transforman en macrófagos, convirtiéndose definitivamente en células espumosas después de haber internalizado las partículas remanentes y otras lipoproteínas modificadas. Recientes estudios sugieren que existen intervenciones efectivas para modular la inflamación posprandial, y de esta forma rebajar el riesgo cardiovascular. Frutas ricas en polifenoles, aceite de oliva virgen, el caroteno y el ejercicio son ejemplos que han demostrado una reducción de la inflamación posprandial. El tratamiento con estatinas y fibratos no solo mejora el perfil lipídico, sino que también rebaja la lipidemia posprandial. Esta revisión describe los recientes conceptos de la inflamación posprandial relacionada con la generación de ateroesclerosis y también trata las intervenciones que pueden influir positivamente en la inflamación posprandial

Influence of lipolysis and fatty acid availability on fuel selection during exercise

The aim of the present study was to investigate the influence of substrate availability on fuel selection during exercise. Eight endurance-trained male cyclists performed 90-min exercise at 70 % of their maximal oxygen uptake in a cross-over design, either in rested condition (CON) or the day after 2-h exercise practised at 70 % of maximal oxygen uptake (EX). Subjects were given a sucrose load (0.75 g kg−1 body weight) 45 min after the beginning of the 90-min exercise test. Lipolysis was measured in subcutaneous abdominal adipose tissue (SCAT) by microdialysis and substrate oxidation by indirect calorimetry. Lipid oxidation increased during exercise and tended to decrease during sucrose ingestion in both conditions. Lipid oxidation was higher during the whole experimental period in the EX group (p = 0.004). Interestingly, fuel selection, assessed by the change in respiratory exchange ratio (RER), was increased in the EX session (p = 0.002). This was paralleled by a higher rate of SCAT lipolysis reflected by dialysate glycerol, plasma glycerol, and fatty acids (FA) levels (p < 0.001). Of note, we observed a significant relationship between whole-body fat oxidation and dialysate glycerol in both sessions (r 2 = 0.33, p = 0.02). In conclusion, this study highlights the limiting role of lipolysis and plasma FA availability to whole-body fat oxidation during exercise in endurance-trained subjects. This study shows that adipose tissue lipolysis is a determinant of fuel selection during exercise in healthy subjects

Evidencia disponible acerca del uso del agonista B3- adrenoceptor selectivo mirabegrón para el tratamiento de la vejiga hiperactiva / Evidence available on the use of the selective B3- adrenoceptor agonist mirabegron for the treatment of overactive bladder

Contexto: Mirabegrón, agonista adrenoreceptor β3, supone el último desarrollo farmacológico para el tratamiento de la vejiga hiperactiva (VH).Objetivo: Presentar la evidencia disponible respecto a la eficacia y tolerancia de mirabegrón y discutir el potencial de dicho tratamiento en nuestro entorno. Adquisición de evidencia: Se revisan 11 estudios llevados a cabo con mirabegrón en pacientes con VH (2 fase II , 9 fase III ), todos en comparación con placebo y 6 de ellos incluyeron también tolterodina como brazo adicional. Se hace mayor énfasis en los principales ensayos fase III llevados a cabo en Europa, EE. UU. y Australia que evalúan la eficacia y seguridad a 12 semanas (NCT00662909, NCT00689104, NCT00912964) y la seguridad a 12 meses (NCT00688688). Se dispone también del análisis combinado de dichos estudios a 12 semanas, enfatizando en la eficacia global (FAS), la eficacia relativa a la incontinencia (FAS- I) y la seguridad (SAF). Más del 50% de los pacientes había abandonado previamente la medicación anticolinérgica para VH, lo que permite también obtener datos acerca de la efectividad de mirabegrón en pacientes tratados previamente con anticolinérgicos. Síntesis de evidencia: Mirabegrón es un fármaco eficaz que muestra una reducción estadísticamente significativa en número de episodios de incontinencia y en frecuencia miccional a partir de la 4.a semana, con mayor porcentaje tanto de pacientes secos como de pacientes con reducción ≥ 50% en número de episodios de incontinencia que placebo. La eficacia de mirabegrón 50 y 100 mg en la reducción en episodios de incontinencia sucede en pacientes nuevos y que han recibido antimuscarínicos, siendo la diferencia media ajustada y la mejora en la frecuencia miccional mayor en pacientes tratados. Su tolerancia es muy similar a placebo, particularmente para los efectos adversos de los antimuscarínicos (boca seca, estreñimiento y visión borrosa). Se aprecia un cambio mínimo no clínicamente significativo en la presión arterial sistólica, en la diastólica y en el pulso. Su eficacia se mantiene a largo plazo. Mirabegrón a dosis de 50 y 100 mg presenta mejoría frente placebo en la satisfacción del paciente, en la calidad de vida relacionada con la salud (HRQoL), en las molestias de síntomas y en la percepción del paciente de la condición vesical (PPBC). En el estudio europeo fase III a 12 semanas tolterodina proporcionó mejoría en menor medida que mirabegrón frente a placebo en la satisfacción del paciente, HRQoL, molestia de síntomas y PPBC (AU)

Context: Mirabegron, the selective β3-adrenoceptor agonist, heralds the latest development for the treatment of overactive bladder (OAB). Objective: To present the evidence available on the efficacy and tolerability of mirabegron and to discuss this treatment's potential in our setting. Evidence acquisition: We reviewed 11 studies conducted with mirabegron in patients with OAB (2 phase II, 9 phase III, all studies were compared to placebo with 6 studies also including tolterodine as an additional arm. Greater emphasis shall be given to the main phase III trials performed in Europe, the USA and Australia evaluating efficacy and safety after 12 weeks (NCT00662909, NCT00689104, NCT00912964) and safety after 12 months (NCT00688688). The combined analyses of these 12-week studies are also available, with emphasis on global efficacy (FAS), efficacy with regard to incontinence (FAS I ) and safety (SAF). More than 50% of patients had previously discontinued anticholinergics medication for OAB, thus allowing us to obtain data on the effectiveness of mirabegron in patients already treated with anticholinergics. Evidence synthesis: Mirabegron is an efficacious drug which presents a statistically significant reduction in the number of incontinence episodes and in urinary frequency as of 4 weeks, with a higher percentage of dry patients and a higher percentage of patients with reduction ≥50% in the number of incontinence episodes than placebo. The efficacy of mirabegron 50 and 100 mg in the reduction of incontinence episodes occurs in de novo patients and who have received antimuscarinics, with adjusted mean difference and improvement in urinary frequency greater in treated patients. Its tolerability is very similar to placebo particularly for the adverse effects of the antimuscarinics (dry mouth, constipation and blurred vision). A minimal, non-clinically significant change is observed in systolic and diastolic blood pressure and pulse. Its efficacy is long-term. Mirabegron at the doses of 50 and 100 mg presents an improvement versus placebo in patient satisfaction, health-related quality of life (HRQoL), symptom bother and patient's perception of bladder condition (PPBC). In the 12-week phase III European study tolterodine deliverred a lesser degree of improvement than mirabegron versus placebo in patient satisfaction, HRQoL, symptom bother and PPBC. Conclusions: Mirabegron is the first of a new class of compounds with a novel mechanism of action that is different to the antimuscarinics. It presents significant and clinically important efficacy in the treatment of the symptoms of OAB. It has advantages with regard to the results described by the patient in treatment satisfaction. Studies on its combined use with anticholinergics are ongoing (AU)

Resveratrol directly affects in vitro lipolysis and glucose transport in human fat cells

Resveratrol is a naturally occurring polyphenol found in many dietary sources and red wine. Recognized as a cancer chemoprevention agent, an anti-inflammatory factor and an antioxidant molecule, resveratrol has been proposed as a potential anti-obesity compound and to be beneficial in diabetes. Most of the studies demonstrating the anti-adipogenic action of resveratrol were performed as long-term treatments on cultured preadipocytes. The aim of this study was to analyse the acute effects of resveratrol on glucose uptake and lipolysis in human mature adipocytes. Samples of subcutaneous abdominal adipose tissue were obtained from overweight humans and immediately digested by liberase. Fat cells were incubated (from 45 min to 4 h) with resveratrol 1 Mu-1 mM. Then, glycerol release or hexose uptake was determined. Regarding lipolysis, the significant effects of resveratrol were found at 100 Mu, consisting in a facilitation of isoprenaline stimulation and an impairment of insulin antilipolytic action. At 1 and 10 Mu, resveratrol only tended to limit glucose uptake. Resveratrol 100 Mu did not change basal glucose uptake but impaired its activation by insulin or by benzylamine. This inhibition was not found with other antioxidants. Such impairment of glucose uptake activation in fat cells may led to a reduced availability of glycerol phosphate and then to a decreased triacylglycerol assembly. Therefore, resveratrol increased triacylglycerol breakdown triggered by Beta-adrenergic activation and impaired lipogenesis. Consequently, our data indicate that resveratrol can be considered as limiting fat accumulation in human fat cells and further support its use for the mitigation of obesity

Adipose tissue lipases and lipolysis

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Tratamiento de adiposidades localizadas mediante técnicas no quirúrgicas / Techniques for the treatment of localized fat without surgery

Introducción: Las técnicas no quirúrgicas para el tratamiento de la grasa localizada tienen la finalidad de disminuir el espesor del tejido adiposo subcutáneo sin necesidad de extracción de la grasa, circunstancia que las diferencia de los procedimientos quirúrgicos. Objetivos: Evaluar la efectividad de las técnicas físicas y químicas (ultrasonidos focalizados de alta intensidad, cavitación, láser lipólisis e hidrolipoclasia con suero hipoosmolar) en el tratamiento de las adiposidades localizadas. Métodos: Se trataron 106 pacientes con adiposidades localizadas en flancos, abdomen y/o caderas. Realizamos los siguientes procedimientos: hidrolipoclasia hipoosmolar, hidrolipoclasia más cavitación, ultrasonidos focalizados de alta intensidad, láser lipólisis (sin aspiración) y cavitación. Se indicaron prendas de compresión durante las 72 horas posteriores a los tratamientos y los pacientes no realizaron dieta ni otros tratamientos. Resultados: Todos los pacientes presentaron disminución de las medidas de circunferencia de cintura y cadera sin cambios significativos en el peso. La disminución del espesor del tejido graso medido con ecografía fue de un 15% en caderas, un 12% en flancos y un23% en abdomen. Discusión: Las técnicas no quirúrgicas para el tratamiento de la grasa localizada ocasionan reducción del espesor del tejido graso tratado. Conclusiones: Los resultados obtenidos nos permiten concluir que estos procedimientos son una alternativa a la liposucción en adiposidades de pequeño volumen, en casos seleccionados y regiones determinadas, suelen ser necesarias varias sesiones y deberían realizarse estudios a largo plazo. Hemos observado un mayor porcentaje de complicaciones con el láser lipólisiss in succión, razón por la cual esta técnica solo debe utilizarse como técnica de liposucción asistida por láser (AU)

Introduction: The new techniques for the treatment of localized fat without surgery take advantage of the application of physical and/or chemical methods that are minimally invasive and can be carried out in an ambulatory way. The aim of these techniques is to diminish the thickness of subcutaneous adipose tissue without needing the extraction of the damaged fat. Objective: To assess physical and/or chemical methods ( ultrasound, laser lipolysis, and hipoosmolarhydrolipoclasia) for body contouring. Methods: 106 patients with localized fat in flanks, abdomen and/or hips were selected. The following procedures were implemented: hipoosmolar hydrolipoclasia, ultrasonic hydrolipoclasia (with cavitation), cavitation, laser lipolysis and high intensity focused ultrasound. All the patients used compressive garments during the 72 hours after the treatment. They neither follow any diet nor other treatments. Results: All the patients presented a decrease in the hip and waist measurements without significant changes in the weight. This loss of fat measurement with B Mode Echography was 15% in the hips, 12% in the flanks and 23% in the abdomen. Discussion: The techniques for the treatment of localized fat without surgery mentioned above are effective in reducing localized adiposities. Conclusion: The results showed that these techniques are effective in reducing localized adiposities. Are an alternative for lipoaspiration in small volume adiposities in selected cases and in defined areas of the body. Given the variability of the responses, several sessions may be required and the patients should be informed about it. A higher percentage of complication was found with laser lipolysis without aspiration that is why this technique should only be used as a lipoaspiration assisted by laser. Further studies should be realized in the future (AU)

Isopropylnorsynephrine is a stronger lipolytic agent in human adipocytes than synephrine and other amines present in Citrus aurantium

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The weight loss observed in consumers of extracts of Citrus aurantium (bitter orange) has been tentatively attributed to the lipolytic and thermogenic effects of the alkaloids abundant in the unripe fruit. Synephrine, octopamine, tyramine, and other alkaloids have been repeatedly identified and quantified in Citrus members of the Rutaceae family or in their extracts incorporated in dietary supplements for weight management. However, there are only scarce reports on their lipolytic action. This study aimed at comparing the acute lipolytic activity of synephrine, octopamine, tyramine, andN-methyltyramine in rat and human adipocytes. Maximal respo (..) (AU)

Lipolisis subcutánea secundaria a infiltración por glucocorticoides / Subcutaneous lipolysis induced by glucocorticoid injections

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Effect of clenbuterol on apoptosis, adipogenesis, and lipolysis in adipocytes

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Clenbuterol, a beta2-adrenergic receptor (Beta2-AR) selective agonist, has been shown to decrease body fat in animals and can induce apoptosis in adipose tissue in mice. We hypothesized that direct actions of a Beta -adrenergic receptor agonist on adipocytes could trigger the observed apoptotic effect. The hypothesis was inspected by investigating the direct effect of clenbuterol on apoptosis,adipogenesis, and lipolysis in vitro using the 3T3-L1 cell line and rat primary adipocytes. Cells were treated with (…) (AU)