¿Cuándo finaliza el tratamiento de un TCA desde el punto de vista dietético nutricional? / When does the treatment of an eating disorder end from the dietary-nutritional point of view?

Objetivos: Este trabajo pretende analizar los consensos actuales acerca de cuándo se establece la finalización del tratamientodietético-nutricional de los TCA, así como qué requisitos se han de cumplir, en el contexto de un tratamiento multidisciplinar. Métodos: Para la elaboración de este trabajo se han consultado fuentes secundarias de información tales como las bases de datoselectrónicas PubMed, SciELO, y Dialnet Plus, en las que hemos introducido diferentes descriptores relacionados con nuestros objetivosy hemos seleccionado nuestros criterios de inclusión, recopilando un total de 20 artículos para su análisis. Resultados: La realidad actual de la recuperación de los TCA se entiende como una restauración del peso y la composición corporalexistiendo escasa evidencia sobre cómo han de ser las intervenciones dietéticas necesarias para mejorar la salud y la alimentación delas personas con trastornos alimentarios. Conclusiones: Uno de los motivos principales parece ser la escasez de estudios sobre la relación entre el comportamiento alimentariode los pacientes que recuperaron el peso, y sus resultados a largo plazo; por lo que parece necesario definir un protocolo dietético derecuperación cualitativo, a largo plazo, y con una menor probabilidad de recaídas.(AU)

Objective: This piece of work pretends to analyze the current consensus about when the completion of the dietary-nutritional treatmentof eating disorders is established, as well as what requirements must be met, in the context of a multidisciplinary treatment. Methods: For the elaboration of this work, secondary sources of information have been consulted, such as the electronic databasesPubMed, SciELO, and Dialnet Plus, in which we have introduced different descriptors related to our objectives and we have selectedour inclusion criteria, compiling a total of 20 articles for analysis. Results: The current reality of recovery from eating disorders is understood as a restoration of weight and body composition, with littleevidence on what the necessary dietary interventions should be like to improve the health and nutrition of people with eating disorders. Conclusions: One of the main reasons seems to be the scarcity of studies on the relationship between the eating behavior of patientswho regained weight, and their long-term results; Therefore, it seems necessary to define a long-term, qualitative recovery dietaryprotocol with a lower probability of relapse.(AU)

Diseño de un programa de prevención de Trastornos de la Conducta Alimentaria en niños / Design of a prevention program for Eating disorders in children

Introducción: En la sociedad actual, la publicidad, las redes sociales, los medios de comunicación bombardean a los usuarios con mensajes que recuerdan cuán importante es mantener una vida saludable para conseguir el cuerpo perfecto. La creciente preocupación por estilos de vida saludables, la presión social para adelgazar; la necesidad de ser aceptado y la preocupación por un ideal estético delgado asociado al éxito social, familiar y profesional podrían ser factores que explicaran esta mayor vulnerabilidad fisiológica a presentar un TCA. Este tipo de enfermedades tienen una etiología multifactorial, es por ello importante centrarnos en corregir estos factores modificables con intervenciones preventivas, tratando patrones de ideales estéticos y culturales, autoestima y autoconcepto, y prácticas dietéticas saludables. Objetivo: El presente trabajo tiene como principal objetivo disminuir la incidencia de problemas relacionados con la conducta alimentaria en los alumnos y alumnas de un centro educativo. Método: Se realizó un diseño piloto. Primero se estudió la evidencia científica existente, relacionada con los estudios de prevención y se diseñó el programa que se pondría en práctica en un grupo minoritario de alumnos de primaria. Si los resultados obtenidos son satisfactorios, el programa de prevención se extrapolará a todas las clases de sexto de primaria del centro educativo. Resultados: Los resultados exponen una idea distinta de un programa de prevención. Conclusiones: Algunos de los temas tratados en este programa son comunes en todos los programas de prevención, ya que se ha estudiado cuáles son los factores de riesgo característicos de estas enfermedades y por tanto los que hay que trabajar de forma más directa (como pueden ser autoestima y autoconcepto, habilidades sociales, términos teóricos de las enfermedades, alimentación saludable, etc) pero en esta propuesta se pretende actualizar información, y trabajar de una manera diferente.(AU)

Introduction: We live in a society where advertising, social networks, the media bombard us with messages that remind us how important it is to maintain a healthy life to achieve the perfect body. The growing concern for healthy lifestyles, social pressure to lose weight, the need to be accepted and the concern for a slim aesthetic ideal associated with social, family and professional success could be factors that explain this greater physiological vulnerability to present an ED. This type of disease has a multifactorial etiology, it is therefore important to focus on correcting these modifiable factors with preventive interventions, treating patterns of aesthetic and cultural ideals, self-esteem and self-concept, and healthy dietary practices. Aim: The main objective of this work is to reduce the incidence of problems related to eating behavior in students of an educational center. Method: The design was a pilot design. First, the existing scientific evidence related to prevention studies was studied and the program was designed, which will be put into practice in a minority group. If the results obtained are satisfactory, the prevention program will be extrapolated to all sixth grade classes of the educational center. Results: The results expose a different idea of a prevention program. Conclusions: Some of the topics covered in this program are common in all prevention programs, since it has been studied which are the characteristic risk factors of these diseases and therefore those that must be worked on more directly (such as self-esteem and self-concept, social skills, theoretical terms of diseases, healthy eating ...) but in this work proposal it is intended to update information, and in a different way.(AU)

Uso de redes sociales y riesgo de padecer TCA en jóvenes / Use of social networks and risk of suffering from TCA in young people

Introducción: Tras el COVID-19 las nuevas tecnologías han tomado aún más relevancia en nuestra sociedad, entre estas, las redes sociales. El uso de estas redes no para de crecer cada año y su uso es cada vez más extendido. Por otro lado, los Trastornos de la Conducta Alimentaria también están a la orden del día, y durante la cuarentena salieron a relucir un considerable número de casos.Objetivo: La siguiente investigación trata de comprobar si existe relación entre el uso de las redes sociales y el riesgo a desarrollar un Trastorno de la Conducta Alimentaria en jóvenes. Método: El diseño fue relacional transversal. Se encuestó de forma online y anónima a 108 jóvenes de entre 18 y 30 años. La encuesta se compuso del instrumento Eating Attitudes Test-26 y preguntas elaboradas por los investigadores sobre el uso de redes sociales y salud. Resultados: Los resultados mostraron una relación significativa entre la frecuencia de uso de redes sociales y tener una experiencia negativa en el uso de las mismas, con el riesgo de padecer un Trastorno de la Conducta Alimentaria. Conclusiones: Tras esta investigación podemos concluir que el uso de redes sociales puede ser un factor de riesgo para el desarrollo de un Trastorno de la Conducta Alimentaria, aunque son necesarias más investigaciones.(AU)

Aim: The following research tries to verify if there is a relationship between the use of social networks and the risk of developing an Eating Disorder in young people. Method: The design was relacional transversal. 108 young people between the ages of 18 and 30 were surveyed online and anonymously. The survey was composed of the Eating Attitudes Test-26 instrument and questions elaborated by the researchers on the use of social networks and health. Results: The results showed a significant relationship between the frequency of use of social networks and have a negative experience in the use of them, with the risk of suffering from an Eating Disorder. Conclusions: After this research we can conclude that the use of social networks can be a risk factor for the development of an Eating Disorder, although more research is necessary.(AU)

¿Es más cara la alimentación saludable? / Is healthy food more expensive?

INTRODUCCIÓN: En ocasiones se ha relacionado el precio de los alimentos con su calidad nutritiva, de forma que los alimentos de menor valor nutritivo resultan los más baratos. Así, la alta disponibilidad de alimentos de bajo coste, podría ser un factor a considerar entre los responsables del aumento de la frecuencia de la obesidad que se observa. OBJETIVO: Realizar una comparativa económica entre el coste de una dieta saludable y otra no saludable. MÉTODO: Estudio descriptivo, transversal. Muestra constituida por 15 sujetos entre 18 y 57 años. Se recogieron los hábitos alimentarios de 3 días, mediante recordatorio de 24 horas y diario dietético. El criterio de dietas saludables o no, se estableció en función de la Guía Alimentaria SENC de diciembre de 2016. Se realizó un cálculo económico del coste diario de la cesta de la compra, un análisis de la media de 3 días del coste de la cesta de la compra y el coste de las comidas realizadas fuera del hogar. Se compararon los costes de la cesta de la compra de quienes tenían una Dieta Saludable y No Saludable. También se tuvo en cuenta en el estudio el IMC de los sujetos. RESULTADOS: Los resultados obtenidos confirman que es más económica una dieta saludable que una no saludable, y que el IMC no tiene una correlación directa y exclusiva con el hecho de seguir una dieta de mayor o menor calidad nutricional. CONCLUSIONES: Si consideramos que el factor económico no es uno de los factores más importante en el hecho de llevar unas pautas nutricionales saludables, sería interesante un estudio posterior con una muestra más amplia y una actuación educativo-nutricional para dar herramientas a la población que les posibilite unas elecciones más adecuadas de alimentos y mayor implicación personal en tiempo, conocimiento de técnicas, etc., más allá del aspecto puramente económico

INTRODUCTION: Occasionally, the price of food has been linked to its nutritional quality so that foods with lower nutritional value are the cheapest. Thus, the high availability of low-priced food could be a factor to consider among the ones responsible for the increased frequency of obesity that is now been observed. OBJECTIVE: The main objective of this study was to make an economic comparison between the cost of healthy eating vs unhealthy eating. METHODS: A cross-sectional descriptive study. The sample was made up of 15 individuals aged 18-57. Eating habits were collected for 3 days via 24- hour dietary recall and diet diary. The criteria for a healthy or unhealthy diet was stablished according to the SENC Food Guidance- December 2016. Daily cost of shopping basket, analysis of the average shopping basket for three days and the cost of food eating outside were made. The cost of shopping basket was compared between healthy and unhealthy eaters. The BMI was also considered in this study. RESULTS: The results obtained confirm that a healthy diet is cheaper than an unhealthy one and that there is not direct and exclusive correlation between the BMI and healthy or unhealthy eating. CONCLUSIONS: If we consider that the economic factor is the most important one regarding healthy eating patterns, further study based on a wider simple and an educational-nutritional intervention would be interesting in order to provide individuals with tools to make possible the most adequate election of the food and a greater personal involvement in time, technical knowledge, etc. beyond the economic aspect

Alimentación familiar: influencia en el desarrollo y mantenimiento de los trastornos de la conducta alimentaria / Family food habits: influence on development and maintenance of eating disorders

Los trastornos de la conducta alimentaria, en adelante TCA, son alteraciones de la conducta relacionada con la alimentación que normalmente se ven influenciados en gran medida por la alimentación del entorno y de la familia. Abordar los factores de riesgo que pueden estar relacionados con la alimentación familiar y que podrían ser desencadenantes de un TCA es clave como prevención. De las diferentes investigaciones de relevantes autores que estudiaron la correlación entre el ámbito familiar y los TCA, con centro en la alimentación familiar, surge el foco de esta revisión, tratando de dar una explicación a los motivos que apuntan a la relación entre alimentación familiar y TCA, destacando los factores de riesgo que se han considerado más influyentes tanto en el desarrollo como en el mantenimiento de los mismos. El objetivo es entender de qué manera el núcleo familiar puede influir sobre estos trastornos dependiendo de sus valores y creencias, la personalidad y relación de cada miembro con la persona afectada o las patologías previas, así como la herencia genética. Los resultados obtenidos fueron mayoritariamente correlacionales, es decir, una familia desestructurada, con altos niveles de ansiedad o estrés, o con presencia de sobrepeso, implicará más riesgo de que algún miembro sufra un TCA en contraposición a aquellas familias con buena comunicación y roles establecidos donde el peso no es importante. Sin embargo, y como se desarrolla a lo largo del trabajo, esto no parece ser un factor que se cumpla en todos los casos. El mantenimiento de estos desórdenes puede variar en función de la implicación que muestre la familia por la recuperación del paciente, la disposición de dicha familia a cambiar sus hábitos y la mejora del ambiente de convivencia

Eating disorders (mainly anorexia nervosa, bulimia nervosa, and binge eating disorder) are eating-related behavioral disturbances that are normally largely influenced by eating environment and family. Thus, addressing risk factors that may be related to family eating and that could be triggers for an eating disorder is key as prevention. From the different investigations in books and publications by great authors that studied the correlation between the family environment and eating disorders, Family Eating has been the focus of this review, trying to give an explanation to the reasons that point to the relationship between family nutrition and the appearance of these disorders, highlighting the risk factors that have been considered most influential both in the development and maintenance of eating disorders. The objective is to understand how the family nucleus can influence these disorders depending on the values and beliefs they have, the personality and relationship of each member with the affected person or previous pathologies, as well as genetic inheritance. The results obtained were mostly correlational, that is, an unstructured family concerned excessively with the figure, with high levels of anxiety or stress and previous overweight pathologies will tend to be more predisposed to a member suffering from an eating disorder than those families with good communication and established roles where weight is not important. However, and as it develops throughout the work, this does not seem to be a factor that is met in all cases. The maintenance of these disorders may vary depending on the family's involvement in the recovery of the patient, the family's willingness to change their habits and the improvement of the coexistence environment

Trastornos de la conducta alimentaria y diabetes mellitus: tratamiento nutricional / Eating disorders and diabetes mellitus: nutritional treatment

El presente trabajo describe las particularidades en el manejo nutricional y la presentación clínica de los pacientes diabéticos con trastornos de la conducta alimentaria. Es importante el diagnóstico precoz de estas comorbilidades, para tomar las medidas necesarias y evitar complicaciones. Los profesionales sanitarios deben estar alerta a los signos de alarma (incremento de HbA1c, cambios de peso, omisión del tratamiento, excesiva preocupación en la calidad y cantidad de comida, etc.). Según algunos estudios, hasta el 60% de los pacientes con Diabetes Mellitus tipo 1 y hasta el 40% de los pacientes con Diabetes Mellitus tipo 2 pueden cumplir criterios de trastornos de la conducta alimentaria (Diabulimia, Trastorno por atracón, Síndrome del comedor nocturno y formas no específicas). El tratamiento debe llevarse a cabo por un equipo interdisciplinar, teniendo como objetivo principal el restablecimiento del peso adecuado y el control de los comportamiento propios de los trastornos de la conducta alimentaria (purgas, omisiones de tratamiento, atracones, restricciones), se debe establecer un plan dietético nutricional progresivo, evitando centrar la atención en el recuento de raciones de hidratos de carbono, sino en la educación nutricional adecuada y en aquellos con insulina asegurar su adecuada administración. Es importante establecer con el paciente objetivos reales (peso, controles glucémicos, HbA1c) y hablar sobre las complicaciones agudas y crónicas de la diabetes con el paciente y la familia. Todavía quedan muchas áreas de estudio para mejorar el tratamiento integral de estos pacientes

This paper describes the special characteristics in nutritional management and clinical presentation of patients with diabetes and eating disorders at the same time. The screening of these two comorbidities is important in order to take the necessary measures and to avoid complications. Professionals should be aware for warning signs (High HbA1c, weight changes, treatment omission , excessive concern about the quality and quantity of meal, etc.). Some studies show that more than 60% of type 1 Diabetes Mellitus and more than 40% of type 2 Diabetes Mellitus meet criteria for eating disorders (Diabulimia, Binge Eating Disorder, Night eating syndrome and non-specific forms). The treatment must be carried out by an interdisciplinary team, with the main objective of restoring adequate weight and avoiding of eating disorders' behavior (purges, treatment omission, binge eating, restrictions), a progressive dietary plan must be established, not to be focus on counting carbohydrate rations, but on adequate nutritional education and on those patients with insulin to ensure its adequate administration. It is important establish real objectives (weight, blood measure test, HbA1c) and to discuss acute and chronic complications of diabetes not only with the patient but with his/her family. There are still many study'areas to improve the comprehensive treatment of these patients

Self-perception of weight and physical fitness, body image perception, control weight behaviors and eating behaviors in adolescents.

INTRODUCTION: self-perception of weight and physical fitness, aesthetic reasons to diet, self-weighing as a way to feel better and body image perception have been related to a constellation of risks to develop both body image dissatisfaction and eating behavior disturbances, especially among adolescents. OBJECTIVES: to analyze weight self-perception and self-reported physical fitness, to explore the links between these variables and weight control behaviors, to explore possible relations among weight self-perception, self-reported physical fitness, dieting, self-weighing frequency and body mass index (BMI)/body image and to analyze the relation between all these variables and different eating behaviors. METHODS: a total of 336 students (mean age of 12.46 ± 2.14; 47.62% females) took part in this study. Different scales were administered (weight self-perception and self-reported physical fitness, dieting, self-weighing frequency, body image perception, eating behaviors) and height and weight were measured in order to obtain the BMI. RESULTS: mean BMI was 20.18 ± 3.58 and 41.14% of participants had overweight/obesity. Among those who perceived themselves as overweight,76.92% were girls. More than 70% of participants reported average or good physical fitness and more boys reported good or excellent physical fitness. Almost 60% of participants who planned to diet for aesthetic reasons were girls, and girls more than boys self-weighed to feel better. BMI was significantly correlated with body image dissatisfaction/restrictive eating. CONCLUSIONS: there are clear links between weight self-perception, body image, dieting, self-weighing and eating behaviors at an age which might be considered as a starting point to eating behavior disturbances.

Self-perception of weight and physical fitness, body image perception, control weight behaviors and eating behaviors in adolescents / Autopercepción del peso y forma física, percepción de la imagen corporal y conductas de control de peso y alimentarias en adolescentes

Introduction: self-perception of weight and physical fitness, aesthetic reasons to diet, self-weighing as a way to feel better and body image perception have been related to a constellation of risks to develop both body image dissatisfaction and eating behavior disturbances, especially among adolescents. Objectives: to analyze weight self-perception and self-reported physical fitness, to explore the links between these variables and weight control behaviors, to explore possible relations among weight self-perception, self-reported physical fitness, dieting, self-weighing frequency and body mass index (BMI)/body image and to analyze the relation between all these variables and different eating behaviors. Methods: a total of 336 students (mean age of 12.46 ± 2.14; 47.62% females) took part in this study. Different scales were administered (weight self-perception and self-reported physical fitness, dieting, self-weighing frequency, body image perception, eating behaviors) and height and weight were measured in order to obtain the BMI. Results: mean BMI was 20.18 ± 3.58 and 41.14% of participants had overweight/obesity. Among those who perceived themselves as overweight,76.92% were girls. More than 70% of participants reported average or good physical fitness and more boys reported good or excellent physical fitness. Almost 60% of participants who planned to diet for aesthetic reasons were girls, and girls more than boys self-weighed to feel better. BMI was significantly correlated with body image dissatisfaction/restrictive eating. Conclusions: there are clear links between weight self-perception, body image, dieting, self-weighing and eating behaviors at an age which might be considered as a starting point to eating behavior disturbances

Introducción: la autopercepción del peso y de la forma física, razones estéticas para hacer dieta, pesarse como método para sentirse mejor y la percepción de la imagen corporal se han relacionado con una constelación de riesgos para desarrollar tanto insatisfacción corporal como alteraciones alimentarias, especialmente en adolescentes. Objetivos: analizar la autopercepción del peso y de la forma física, explorar los vínculos entre estas variable y conductas de control de peso, explorar posibles relaciones entre la autopercepción del peso y de la forma física, realización de dietas, frecuencia con la que se pesan los adolescentes e índice de masa corporal (IMC)/imagen corporal, así como la relación de todo ello con diferentes conductas alimentarias. Resultados: el IMC medio fue de 20,18 ± 3,58 y el 41,14% de los participantes presentaba sobrepeso/obesidad. Entre quienes se percibían con sobrepeso, el 76,92% eran chicas. Más del 70% de los participantes decían estar en una buena forma física o en la media y eran más los chicos los que decían estar en buena o excelente forma física. Casi el 60% de los participantes que planeaban hacer dieta por razones estéticas eran chicas y ellas más que los chicos se pesaban para sentirse mejor. El IMC correlacionó significativamente con la subescala imagen corporal/ ingesta restrictiva. Conclusiones: existen claros vínculos entre autopercepción ponderal, imagen corporal, realización de dietas, pesarse y conductas alimentarias en una edad que podría considerarse como un punto de partida para la presentación de alteraciones alimentarias

Loss of Pancreas upon Activated Wnt Signaling Is Concomitant with Emergence of Gastrointestinal Identity.

Organ formation is achieved through the complex interplay between signaling pathways and transcriptional cascades. The canonical Wnt signaling pathway plays multiple roles during embryonic development including patterning, proliferation and differentiation in distinct tissues. Previous studies have established the importance of this pathway at multiple stages of pancreas formation as well as in postnatal organ function and homeostasis. In mice, gain-of-function experiments have demonstrated that activation of the canonical Wnt pathway results in pancreatic hypoplasia, a phenomenon whose underlying mechanisms remains to be elucidated. Here, we show that ectopic activation of epithelial canonical Wnt signaling causes aberrant induction of gastric and intestinal markers both in the pancreatic epithelium and mesenchyme, leading to the development of gut-like features. Furthermore, we provide evidence that ß -catenin-induced impairment of pancreas formation depends on Hedgehog signaling. Together, our data emphasize the developmental plasticity of pancreatic progenitors and further underscore the key role of precise regulation of signaling pathways to maintain appropriate organ boundaries.

Effect of thermal processing on the profile of bioactive compounds and antioxidant capacity of fermented orange juice.

Previously, we reported that alcoholic fermentation enhanced flavanones and carotenoids content of orange juice. The aim of this work was to evaluate the influence of pasteurization on the qualitative and quantitative profile of bioactive compounds and the antioxidant capacity of fermented orange juice. Ascorbic acid (203 mg/L), total flavanones (647 mg/L), total carotenoids (7.07 mg/L) and provitamin A (90.06 RAEs/L) values of pasteurized orange beverage were lower than those of fermented juice. Total phenolic remained unchanged (585 mg/L) and was similar to that of original juice. The flavanones naringenin-7-O-glucoside, naringenin-7-O-rutinoside, hesperetin-7-O-rutinoside, hesperetin-7-O-glucoside and isosakuranetin-7-O-rutinoside, and the carotenoids karpoxanthin and isomer, neochrome, lutein, ζ-carotene, zeaxanthin, mutatoxanthin epimers, ß-cryptoxanthin and auroxanthin epimers were the major compounds. Pasteurization produced a decrease in antioxidant capacity of fermented juice. However, TEAC (5.45 mM) and ORAC (6353 µM) values of orange beverage were similar to those of original orange juice. The novel orange beverage could be a valuable source of bioactive compounds with antioxidant capacity and exert potential beneficial effects.

Consumption of orange fermented beverage reduces cardiovascular risk factors in healthy mice.

The consumption of fruits prevents the risk of cardiovascular diseases. Alcoholic fermentation has been carried out in fruits resulting in products which provide high concentration of bioactive compounds and variable alcohol content. The aim of this study was to assess the potential beneficial effect of an orange beverage obtained by alcoholic fermentation and pasteurization of orange juice on cardiovascular risk biomarkers. For this purpose, four mice groups (n = 8) ingested orange beverage (equivalent volume to 250 mL/day in human), orange juice, alcoholic solution (at the proportional amount of orange beverage) or water during 12 weeks. The equivalent amount to double serving of orange beverage (500 mL/day) was administered to mice in a subsequent intervention, and a control group was also evaluated. Orange beverage consumption increased levels of glutathione and uric acid, improved lipid profile, decreased oxidized LDL and maintained levels of IL-6 and C-reactive protein. Synergistic effects between the bioactive compounds and the alcohol content of orange beverage may occur. The intake of double serving also increased antioxidant enzyme activities, bilirubin content and plasma antioxidant capacity. These results suggest that orange beverage may produce greater protection against cardiovascular risk factors than orange juice in healthy mice.

Fermented orange juice: source of higher carotenoid and flavanone contents.

The intake of bioactive compounds and moderate alcohol decreases the risk of cardiovascular diseases. These effects could be joined in a beverage created by a controlled alcoholic fermentation of orange juice. The influence of controlled alcoholic fermentation on the bioactive compound profile of orange juice has not been previously evaluated, and this is the purpose of the present study. Total and individual flavanones and carotenoids significantly increased throughout the fermentation. The reason for this was an enhanced extraction of these compounds from the pulp. Besides, the potential bioavailability of flavanones increased due to a higher content of hesperetin-7-O-glucoside (2-fold higher at the end of the fermentation process). Ascorbic acid did not undergo a significant change, and only total phenolics decreased. Antioxidant capacity was also evaluated. TEAC and FRAP values remained constant throughout the process. However, ORAC and DPPH values significantly increased. Correlation analysis concluded that the increase in ORAC and DPPH values could be due to enhancement of flavanones.

TAK1 activates AMPK-dependent cytoprotective autophagy in TRAIL-treated epithelial cells.

The capacity of tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) to trigger apoptosis preferentially in cancer cells, although sparing normal cells, has motivated clinical development of TRAIL receptor agonists as anti-cancer therapeutics. The molecular mechanisms responsible for the differential TRAIL sensitivity of normal and cancer cells are, however, poorly understood. Here, we show a novel signalling pathway that activates cytoprotective autophagy in untransformed human epithelial cells treated with TRAIL. TRAIL-induced autophagy is mediated by the AMP-activated protein kinase (AMPK) that inhibits mammalian target of rapamycin complex 1, a potent inhibitor of autophagy. Interestingly, the TRAIL-induced AMPK activation is refractory to the depletion of the two known AMPK-activating kinases, LKB1 and Ca(2+)/calmodulin-dependent kinase kinase-beta, but depends on transforming growth factor-beta-activating kinase 1 (TAK1) and TAK1-binding subunit 2. As TAK1 and AMPK are ubiquitously expressed kinases activated by numerous cytokines and developmental cues, these data are most likely to have broad implications for our understanding of cellular control of energy homoeostasis as well as the resistance of untransformed cells against TRAIL-induced apoptosis.

Statins activate a mitochondria-operated pathway of apoptosis in breast tumor cells by a mechanism regulated by ErbB2 and dependent on the prenylation of proteins.

Statins are inhibitors of the mevalonate synthesis pathway that induce apoptosis in tumor cells although the apoptotic mechanism activated by statins remains to be elucidated. We have examined the role of the mitochondria-operated pathway of apoptosis in the cell death induced by statins in breast tumor cells and its regulation by protein prenylation and ErbB2 overexpression. Lovastatin treatment down-regulates the expression of Bcl-2 and activates apoptosis through a mitochondria-operated, ErbB2- regulated mechanism. Apoptosis induced by statins is independent of their effects on cholesterol synthesis and involves protein prenylation. Our results indicate that prenylation of apoptosis-regulating proteins is a key event in the survival of breast tumor cells and this requirement could be circumvented in cells overexpressing the oncogene ErbB2.