The potential role of apigenin in the enhancement of the antioxidant adaptation to exercise by bioactive dietary compounds

Oxidative stress (OS) occurs when the antioxidant defense system is overwhelmed by the predominance of reactive oxygen species (ROS) and pro-oxidant factors. Several diseases such as hypertension, insulin resistance, type 2 diabetes mellitus and neurodegenerative diseases are characterized by chronic OS. Physical exercise constitutes an affordable tool to prevent or ameliorate these conditions. However, during physical activity, acute ROS are produced inducing an activation in peroxisome proliferator activated receptor-Gamma Coactivator-1alpha (PGC-1α), and nuclear factor erythroid-2 related factor 2 (Nrf2), PGC-1α/Nrf2 pathway. This signaling pathway facilitates interaction with antioxidant response elements (ARE), thereby initiating an upregulation in the expression of antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX) and mitochondrial biogenesis. In both cases, whether involving healthy animals or individuals engaged in physical exercise, supplementation with antioxidant scavengers leads to a reduction in the expression and activity of PGC-1α, SOD, CAT, and GPX across various tissues, which is not observed with indirect antioxidants. The preventive role of physical exercise against chronic OS is avoided when executed in conjunction with supplementation of scavenger antioxidants. However, similar to exercise, the indirect antioxidant apigenin can activate the PGC1-α/Nrf2 signaling pathway. Here, we summarize evidence supporting apigenin as a non-nutritional supplement that could enhance the adaptive effects of exercise, improving the endogenous antioxidant defense. Therefore, apigenin could be an interesting supplement to enhance the endogenous antioxidant adaptation induced by exercise in healthy subjects, but also to improve the effectiveness of exercise to prevent oxidative stress-associated diseases.

El estrés oxidativo (OS) ocurre cuando el sistema de defensa antioxidante es sobrepasado por el predominio de especies reactivas de oxígeno (ROS) y factores prooxidantes. Varias enfermedades como la hipertensión, la resistencia a la insulina, la diabetes mellitus tipo 2 y enfermedades neurodegenerativas se caracterizan por un OS crónico. El ejercicio físico constituye una herramienta asequible para prevenir o mejorar estas enfermedades. Sin embargo, durante la actividad física, se producen ROS agudas que inducen una activación en la vía PGC-1α/Nrf2. Esta vía de señalización facilita la interacción con los elementos de respuesta antioxidante (ARE), iniciando así una regulación que permite la expresión de enzimas antioxidantes, incluidas SOD, CAT, GPX y biogénesis mitocondrial. En ambos casos, ya sea que se trate de animales sanos o de individuos que practican ejercicio físico, la suplementación con antioxidantes "scavengers" conduce a una reducción en la expresión y actividad de PGC-1α, SOD, CAT y GPX en varios tejidos, lo que no se observa con antioxidantes "indirectos". El papel preventivo del ejercicio físico contra el OS crónico se atenúa cuando se realiza en conjunto con la suplementación de antioxidantes "scavengers". Sin embargo, de manera similar al ejercicio, la apigenina es un antioxidante "indirecto" que puede activar la vía de señalización PGC1-α/Nrf2. Aquí, resumimos la evidencia que respalda a apigenina como un suplemento no-nutricional que podría mejorar los efectos adaptativos del ejercicio, mejorando la defensa antioxidante endógena de sujetos sanos que no tienen suficiente tiempo para hacer ejercicio.

Effects on Fetal Metabolic Programming and Endocannabinoid System of a Normocaloric Diet during Pregnancy and Lactation of Female Mice with Pregestational Obesity.

Fetal programming provides explanatory mechanisms for the currently high prevalence of gestational obesity. The endocannabinoid system (ECS) participates in the regulation of energy balance, and with a high-fat diet (HFD), it is overactivated. The aim of this study was to determine the effects of a nutritional intervention during pregnancy and lactation on obese female progenitors, on metabolic alterations of the offspring and on the involvement of ECS. Female mice (C57/BL/6-F0), 45 days old, and their offspring (males) were separated according to type of diet before and during gestation and lactation: CON-F1: control diet; HFD-F1 group: HFD (fat: 60% Kcal); INT-F1 group: HFD until mating and control diet (fat: 10% Kcal) afterward. Glucose tolerance and insulin sensitivity (IS) were tested at 2 and 4 months. At 120 days, mice were sacrificed, plasma was extracted for the determination of hormones, and livers for gene expression and the protein level determination of ECS components. INT-F1 group presented a lower IS compared to CON-F1, and normal levels of adiponectin and corticosterone in relation to the HFD-F1 group. The intervention increased hepatic gene expression for fatty-acid amide hydrolase and monoacylglycerol lipase enzymes; however, these differences were not observed at the protein expression level. Our results suggest that this intervention model normalized some hormonal parameters and hepatic mRNA levels of ECS components that were altered in the offspring of progenitors with pre-pregnancy obesity.

Targeting Mitochondria for the Prevention and Treatment of Nonalcoholic Fatty Liver Disease: Polyphenols as a Non-pharmacological Approach.

SCOPE: Nonalcoholic fatty liver disease (NAFLD) has a high and growing prevalence globally. Mitochondria are fundamental in regulating cell energy homeostasis. Nevertheless, mitochondria control mechanisms can be exceeded in this context of energy overload. Damaged mitochondria worsen NAFLD progression. Diet and lifestyle changes are the main recommendations for NAFLD prevention and treatment. Some polyphenols have improved mitochondrial function in different NAFLD and obesity models. OBJECTIVE: The study aims to discuss the potential role of polyphenols as a nonpharmacological approach targeting mitochondria to prevent and treat NAFLD, analyzing the influence of polyphenols' chemical structure, limitations and clinical projections. METHODS: In vivo and in vitro NAFLD models were considered. Study searches were performed using the following keywords: nonalcoholic fatty liver disease, liver steatosis, mitochondria, mitochondrial activity, mitochondrial dynamics, mitochondrial dysfunction, mitochondrial morphology, mitochondrial cristae, fusion, fission, polyphenols, flavonoids, anthocyanins, AND/OR bioactive compounds. CONCLUSION: Polyphenols are a group of diverse bioactive molecules whose bioactive effects are highly determined by their chemical structure. These bioactive compounds could offer an interesting non-pharmacological approach to preventing and treating NAFLD, regulating mitochondrial dynamics and function. Nevertheless, the mitochondria' role in subjects with NAFLD treatment is not fully elucidated. The dosage and bioavailability of these compounds should be addressed when studied.

Potencial efecto terapéutico de los polifenoles obtenidos de la cáscara de granada en la esteatosis hepática

RESUMEN Antecedentes: La enfermedad por hígado graso no alcohólico (EHGNA) tiene una elevada prevalencia a nivel mundial, y puede ir desde la esteatosis simple hasta hepatocarcinoma. Su origen es multifactorial, siendo la dieta poco saludable un factor clave en su patogenia y progresión. Los polifenoles son antioxidantes que han mostrado beneficios en el tratamiento de la EHGNA. Una fuente emergente de estos compuestos son los residuos agroindustriales, entre ellos, la cáscara de granada. La cáscara de granada tiene un alto contenido de polifenoles, específicamente de elagitaninos. Su extracto fenólico (extracto de cáscara de granada; ECG) ha mostrado efectos promisorios a nivel metabólico. Sin embargo, su uso presenta algunas limitantes que deben ser consideradas antes de recomendar su ingesta mediante alimentos funcionales o nutracéuticos para prevención o tratamiento de EHGNA. Objetivo: Discutir a partir de datos obtenidos en estudios in vitro y modelos animales, el potencial terapéutico de los polifenoles obtenidos de la cáscara de granada para prevención y tratamiento de la EHGNA. Metodología: Se realizó una búsqueda bibliográfica en bases de datos PubMed y Web of Science (2015 a la fecha) de estudios en modelos de esteatosis hepática in vitro y en animales, además de ensayos clínicos relacionados. Conclusión: Existen datos promisorios sobre el uso del ECG en alteraciones metabólicas propias de la EHGNA y esteatosis hepática, principalmente a nivel de perfil lipídico. Se deben discutir las dosis y formas de administración, con el fin de mejorar su estabilidad y biodisponibilidad. Se requieren ensayos clínicos controlados que confirmen los efectos en humanos.

ABSTRACT Background: Nonalcoholic fatty liver disease (NAFLD) has a high prevalence worldwide and can range from simple steatosis to hepatocarcinoma. Its causes are multifactorial, with an unhealthy diet being a key factor in its pathogenesis and progression. Polyphenols are antioxidants that have shown benefits in treating NAFLD. An emerging source of these compounds is agro-industrial by-products, including pomegranate peels. Pomegranate peels are high in polyphenols, specifically ellagitannins. Its polyphenolic extract (PPE) has shown promising metabolic benefits. However, its use has some limitations that must be considered before recommending its intake through functional foods or nutraceuticals to prevent or treat NAFLD. Objective: This article aims to discuss, using results from in vitro studies and animal models, the therapeutic potential of polyphenols obtained from pomegranate peels to prevent and treat NAFLD. Methods: A bibliographic search was carried out in PubMed and Web of Science databases (2015 to date) of in vitro and animal model studies of hepatic steatosis, in addition to related clinical trials. Conclusion: There are promising data on the use of PPE in metabolic disorders typical of NAFLD and hepatic steatosis, mainly improving lipid profile. Doses and vehicles of administration should be discussed to improve stability and bioavailability. Controlled clinical trials are required to confirm the effects in humans.

Effects of Polyphenols in Aging and Neurodegeneration Associated with Oxidative Stress.

Aging is defined as the functional loss of tissues and organs over time. This is a biological, irreversible, progressive, and universal process that results from genetic and environmental factors, such as diet, physical activity, smoking, harmful alcohol consumption, and exposure to toxins, among others. Aging is a consequence of molecular and cellular damage built up over time. This damage begins with a gradual decrease in physical and mental capacity, thus increasing the risk of neurodegenerative diseases such as Alzheimer's and Parkinson's disease. Neuronal, functional, and structural damage can be explained by an imbalance among free radicals, reactive oxygen species, reactive nitrogen species, and antioxidants, which finally lead to oxidative stress. Due to the key role of free radicals, reactive oxygen species, and reactive nitrogen species, antioxidant therapy may reduce the oxidative damage associated with neurodegeneration. Exogenous antioxidants are molecules that may help maintain the balance between the formation and elimination of free radicals, thus protecting the cell from their toxicity. Among them, polyphenols are a broad group of secondary plant metabolites with potent antioxidant properties. Here, we review several studies that show the potential role of polyphenol consumption to prevent, or slow down, harmful oxidative processes linked to neurodegenerative disorders.

El consumo de un extracto de calafate (Berberis microphylla) modifica marcadores de respuesta inmune en ratones delgados y obesos

RESUMEN La obesidad ha sido identificada como factor de riesgo de severidad de infecciones respiratorias. Apoyar la respuesta inmune en sujetos obesos es de interés. El presente trabajo evaluó el efecto del consumo de un extracto de calafate sobre marcadores de respuesta inmune en ratones delgados y obesos. Ratones C57BL/6J machos fueron expuestos por 82 días a dieta estándar (DE) y alta en grasas (DAG). A un subgrupo de ambos grupos, se les administró 50 y 100 mg [polifenoles totales]/kg peso de animal/día, de extracto, en las últimas dos semanas. Se evaluó expresión génica y secreción de marcadores de respuesta inmune, en tejido pulmonar y plasma. Se observó un efecto del tratamiento con extracto en la expresión de IFN-ϓ. Se observaron efectos inducidos por la DAG y el tratamiento con extracto de manera independiente, en la expresión de IL-12. Se observó un efecto global de la DAG sobre IFN-ϓ plasmático, específicamente una disminución en animales alimentados con DAG. Se observó una interacción entre la dieta y el tratamiento con extracto sobre IL-12 plasmática. El tratamiento utilizado modula marcadores que activan la respuesta inmune ante infecciones respiratorias principalmente de origen viral, en animales delgados y obesos.

ABSTRACT Obesity has been identified as a risk factor for severity of respiratory infections. Thus, the support of the immune response in obese subjects is of interest. The present work evaluated the effect of the consumption of a calafate extract on markers of the immune response in lean and obese mice. Male C57BL/6J mice were exposed for 82 days to a standard or a high-fat diet (HFD). A subgroup of both groups was given 50 and 100 mg [total polyphenols]/kg body weight/day of extract in the last two weeks. Gene expression and secretion of immune response markers were evaluated in lung tissue and plasma. An effect of extract treatment on IFN-ϓ expression was observed. Effects induced by the HFD and treatment with extract were observed independent of the expression of IL-12. An overall effect of the HF diet on plasma IFN-ϓ was observed, specifically a decrease in animals fed the HFD. An interaction between diet and extract treatment was observed over plasma IL-12. The treatment used modulates markers that activate the immune response to respiratory infections, mainly of viral origin, in lean and obese animals.

Polyphenols and their anti-obesity role mediated by the gut microbiota: a comprehensive review.

Obesity is a global public health problem that results in chronic pathologies such as diabetes, cardiovascular diseases, and cancer. The treatment approach based on energy restriction and promotion of physical activity is ineffective in the long term. Due to the high prevalence of this pathology, complementary treatments such as brown adipose tissue activation (BAT) and white adipose tissue browning (WAT) have been proposed. Dietary polyphenols are plant secondary metabolites that can stimulate browning and thermogenesis of adipose tissue. They have also been shown to prevent body weight gain, and decrease systemic inflammation produced by high-fat diets. Ingested dietary polyphenols that reach the colon are metabolized by the gut microbiota (GM), regulating its composition and generating a great array of metabolites. GM is involved in the production of short chain fatty acids and secondary bile salts that regulate energetic metabolism. The alteration in the composition of GM observed in metabolic diseases such as obesity and type 2 diabetes can be attenuated by polyphenols. Recent studies support the hypothesis that GM would mediate WAT browning and BAT thermogenesis activation induced by polyphenol administration. Together, these results indicate that GM in the presence of polyphenols plays a fundamental role in the control of obesity possible through BAT activation.

Zinc Supplementation and Strength Exercise in Rats with Type 2 Diabetes: Akt and PTP1B Phosphorylation in Nonalcoholic Fatty Liver.

Type 2 diabetes mellitus (T2D) is a metabolic disorder caused by chronic hyperglycemia due to a deficiency in the secretion and/or action of insulin. Zinc (Zn) supplementation and strength exercise increases insulin signaling. We evaluate the effect of Zn supplementation and strength exercise on insulin resistance in the liver of rats with diet-induced T2D through the study of phosphorylation of Akt and protein tyrosine phosphatase 1B (PTP1B). Rats were fed with a high-fat diet (HFD) for 18 weeks to induce T2D and then assigned in four experimental groups: HFD, HFD-Zn (Zn), HFD-strength exercise (Ex), and HFD-Zn/strength exercise (ZnEx) and treated during 12 weeks. Serum Zn, lipid profile, transaminases, glucose, and insulin were measured. In the liver with/without insulin stimuli, total and phosphorylated Akt (pAktSer473) and PTP1B (pPTP1BSer50) were determined by western blot. Hepatic steatosis was evaluated by histological staining with red oil and intrahepatic triglyceride (IHTG) content. There were no differences in biochemical and body-related variables. The ZnEx group showed a higher level of pAkt, both with/without insulin. The ZnEx group also showed higher levels of pPTP1B with respect to HFD and Zn groups. The ZnEx group had higher levels of pPTP1B than groups treated with insulin. Liver histology showed a better integrity and less IHTG in Ex and ZnEx with respect to the HFD group. The Ex and ZnEx groups had lower IHTG with respect to the HFD group. Our results showed that Zn supplementation and strength exercise together improved insulin signaling and attenuated nonalcoholic liver disease in a T2D rat model.

Microencapsulated pomegranate peel extract induces mitochondrial complex IV activity and prevents mitochondrial cristae alteration in brown adipose tissue in mice fed on a high-fat diet.

Pomegranate peel is an agro-industrial residue obtained after fruit processing with high total polyphenol (TP) content, making it an attractive by-product for its reuse. Pomegranate peel extract (PPE) and its bioactive compounds have shown positive effects on obesity models. Effects on favouring mitochondrial biogenesis and function have also been described. However, once phenolic compounds are extracted, their stability can be affected by diverse factors. Microencapsulation could improve PPE stability, allowing its incorporation into functional foods. Nevertheless, studies on the potential biological effects of PPE microparticles (MPPE) in obesity models are lacking. This study aims to evaluate the effect of MPPE on brown adipose tissue (BAT) mitochondrial structure and function and metabolic alterations related to obesity in mice fed a high-fat diet (HFD). PPE was microencapsulated by spray drying using inulin (IN) as a wall material and physically-chemically characterised. Eight-week-old male C57BL/6J mice (n 40) were randomly distributed into five groups: control diet (CD), HFD, HFD + IN, HFD + PPE (50 mg/kg per d TP) and HFD + MPPE (50 mg/kg per d TP), for 14 weeks. A glucose tolerance test and indirect calorimetry were conducted. Blood and adipose tissue samples were obtained. MPPE supplementation prevented HFD-induced body weight gain (P < 0·001), fasting glycaemia (P = 0·007) and total cholesterol rise (P = 0·001). MPPE resulted in higher BAT mitochondrial complex IV activity (P = 0·03) and prevented HFD-induced mitochondrial cristae alteration (P = 0·02). In conclusion, MPPE prevented HFD-induced excessive body weight gain and associated metabolic disturbances, potentially by activating complex IV activity and preserving mitochondrial cristae structure in BAT in mice fed with a HFD.

Vitamina D, miR-21 y marcadores de apoptosis en pacientes con diabetes tipo I / Vitamin D, miR-21 and apoptosis markers in patients with type 1 diabetes

La diabetes Tipo 1 (DT1) es una compleja enfermedad autoinmune con una etiología aún desconocida. La vitamina D ha sido ampliamente estudiada debido a su potencial terapéutico en los potenciales nuevos casos de DT1. Por otra parte, los microARNs (miRs) han sido propuestos como posibles biomarcadores en diversos procesos biológicos como en la apoptosis e inflamación. El objetivo de este estudio fue evaluar el efecto de la suplementación con vitamina D sobre el perfil de expresión del miR-21 y marcadores de apoptosis tales como: BCL2, STAT3, TIPE2 y DAXX, en células mononucleares periféricas provenientes de pacientes con DT1 y sujetos controles. RESULTADOS: El perfil de expresión de miR-21 se encontró disminuido en los pacientes con DT1 en comparación con los controles. La expresión relativa de BCL2 se encontró aumentada en controles al comparar con pacientes DT1 en todas las condiciones experimentales. La expresión relativa de DAXX mostró un perfil de expresión diferencial al comparar pacientes con DT1 versus controles (p=0.006). CONCLUSIÓN: El estímulo con vitamina D parece tener un posible efecto regulador sobre los genes BCL2 y DAXX.

Type 1 diabetes (T1D) is a complex chronic autoimmune disease. Vitamin D has been one of the most studied therapeutic potential outbreaks related to T1D. Specific miRNAs have been proposed as potential biomarkers in several biological processes as apoptosis and inflammation. The aim of this study was to evaluate the effect of vitamin D on the expression profiles of miR-21 and apoptotic markers BCL2, STAT3, TIPE2 and DAXX, in PBMCs from T1D patients and control subjects. RESULTS: miR-21 expression was increased in controls regarding T1D patients. BCL2 was increased in controls compared to T1D patients in all experimental conditions. DAXX showed different expression patterns between T1D patients and controls (p=0.006). CONCLUSION: Vitamin D showed a possible regulation effect on apoptosis markers mainly through the regulation of BCL2 and DAXX

Body fat composition and miR-378 expression profiling in patients with type 1 diabetes.

PURPOSE: Type 1 diabetes (T1D) is an autoimmune disease that involves genetic, epigenetic, and environmental factors. Change in body composition is a potential mechanism for explaining the increased incidence of T1D. Micro RNA-378 (miRNA-378) is a positive regulator of adipogenesis that has yet to be studied in such patients. This study aims to evaluate the miRNA-378 expression profile in peripheral mononuclear cells of T1D patients and controls and to determine its possible association with levels of body fat, interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α). METHODS: Twenty-four T1D subjects and 20 controls under 18 years of age without autoimmune diseases were studied. miRNA-378 expression profile was determined by TaqMan probes. Body composition was determined by multifrequency bioimpedance. IL-6 and TNF-α serum levels were determined by LUMINEX. AntiGAD65, anti-IA2, and anti-ZnT8 antibodies were quantified in serum by enzyme immunoassays. Statistical significance was considered P<0.05. RESULTS: Similar body mass index and body fat (kg) were observed between the T1D and control subjects (P=0.55 and P=0.69, respectively). The miRNA-378 expression profile was significantly higher in T1D patients compared with the controls (P<0.05). Lower miRNA-378 expression in prepubertal controls was observed compared to pubertal controls, prepubertal T1D, and pubertal T1D (P<0.05). AntiGAD65, AntilA2, and AntiZnT8 were positively correlated with miRNA-378 (P=0.002, P=0.053, and P=0.007). No statistically significant correlation was observed between miRNA-378 expression and IL-6, TNF-α, or body fat. CONCLUSION: Elevated miRNA-378 expression in T1D patients compared with controls is linked to pubertal stage but is not associated with proinflammatory status or body composition.

Overnutrition in Infants Is Associated With High Level of Leptin, Viral Coinfection and Increased Severity of Respiratory Infections: A Cross-Sectional Study.

Objective: To investigate the relationship of overnutrition (obese and overweight) with severity of illness in children hospitalized with acute lower respiratory infections (ALRIs), frequency of viral coinfections and leptin levels. Methods: We studied 124 children <2 years old that were hospitalized for ALRI. Nutritional status was calculated by z-scores according to weight-for-age z-scores, length or height-for-age z-scores, and weight-for-height z-scores. Nasopharyngeal aspirates (NPAs) were obtained and viral respiratory pathogens were identified using reverse transcription polymerase chain reactions (RT-PCR). Respiratory syncytial virus (RSV) load was assessed using quantitative RT-PCR. NPA and plasma leptin level were measured. Clinical data and nutritional status were recorded, and patients were followed up until hospital discharge. Viral coinfection was defined as the presence of two or more viruses detected in the same respiratory sample. Severity of illness was determined by length of hospitalization and duration of oxygen therapy. Results: Children with overnutrition showed a greater frequency of viral coinfection than those with normal weight (71% obese vs. 37% normal weight p = 0.013; 68% overweight vs. 37% normal weight p = 0.004). A lower RSV load was found in obese (5.91 log10 copies/mL) and overweight children (6.49 log10 copies/mL) compared to normal weight children (8.06 log10 copies/mL; p = 0.021 in both cases). In multivariate analysis, obese, and overweight infants <6 months old were associated with longer hospital stays (RR = 1.68; CI: 1.30-2.15 and obese: RR = 1.68; CI: 1.01-2.71, respectively) as well as a greater duration of oxygen therapy (RR = 1.80; IC: 1.41-2.29 and obese: RR = 1.91; CI: 1.15-3.15, respectively). Obese children <6 months showed higher plasma leptin level than normal weight children (7.58 vs. 5.12 ng/µl; p <0.046). Conclusions: In infants younger than 6 months, overnutrition condition was related to increased severity of infections and high plasma leptin level. Also, children with overnutrition showed a greater frequency of viral coinfection and low RSV viral load compared to normal weights children. These findings further contribute to the already existent evidence supporting the importance of overnutrition prevention in pediatric populations.

Caracterización de extractos de piel y hojas de Persea americana Mill. y analisis in vitro de sus potenciales propiedades anti-inflamatorias / Characterization of Persea americana Mill. peels and leaves extracts and analysis of its potential in vitro anti-inflammatory properties

Existe una tendencia mundial de incremento en prevalencia de enfermedades no transmisibles, que se caracterizan por un estado pro-inflamatorio crónico. Por lo tanto, es importante estudiar la relación entre alimentos y salud. La palta (Persea americana), sobresale en la industria por su valor nutricional. El procesamiento de la palta genera gran cantidad de subproductos, que contienen bioactivos con propiedades beneficiosas, como polifenoles. El objetivo del presente trabajo fue caracterizar cuatro extractos de palto (acuoso e hidroalcohólico; de hoja y de cáscara) y analizar sus posibles propiedades anti-inflamatorias in vitro. Fueron determinados polifenoles totales (con el método de Folin­Ciocalteau) y capacidad antioxidante (por FRAP y DPPH) de los extractos. Las propiedades anti-inflamatorias de los extractos fueron determinadas por la liberación de NO y de TNF-, y por la expresión génica de TNF-. Los resultados indican que los extractos hidroalcohólicos presentan más polifenoles (p<0,001) y capacidad antioxidante (p<0,001, por FRAP) que los acuosos. Mas aún, observamos que los extractos hidroalcohólicos de hojas presentaron mayores efectos anti-inflamatorios in vitro, especialmente el hidroalcohólico de hoja en liberación de NO (p<0,001, frente a tratamiento con LPS), acuosos e hidroalcohólicos en liberación de TNF- (p<0,05), y solo los hidroalcohólicos en la expresión de TNF- (p<0,01). En conclusión, los extractos hidroalcohólicos de palto, y especialmente el de hoja, presentan propiedades anti-inflamatorias in vitro que pueden ser consideradas para aplicaciones en mejoría de salud humana.

There is a worldwide trend of increasing prevalence of non-communicable diseases characterized by a chronic inflammatory state. Therefore, it is important to study the relationship between food and health. Avocado (Persea americana) stands out in food industry for its nutritional value. Industrials process of avocado generates a large number of by-products, which contain phytochemical compounds with antioxidant properties, such as polyphenols. The objective of the present research was to characterize four aqueous and hydroalcoholic extracts from avocado leaves and peels and analyze it possible anti-inflammatory properties in vitro. Total polyphenol content (with the Folin-Ciocalteau method) and antioxidant capacity (by FRAP and DPPH) were determined. Extracts inflammatory features were measured by NO and TNF- release, and by TNF- gene expression. Our results indicated that hydroalcoholic extracts present higher total polyphenol content (p<0.001) and antioxidant capacity (p<0.001, by FRAP) than the aqueous ones. Furthermore, we report that hydroalcoholic leaves extract presented greater in vitro anti-inflammatory effect, especially the leave hydroalcoholic regarding NO release (p<0.001, against LPS treatment), aqueous and hydroalcoholics regarding TNF- release (p<0.05), and only the hydroalcoholic in the TNF- gene expression (p<0.01). In conclusion, the avocado hydroalcoholic extracts, and especially from leaves, present in vitro anti-inflammatory features that might be considered for human health improvement applications.

Obesidad parental y modificaciones epigenéticas en la descendencia / Parental obesity and epigenetic modifications in offspring

RESUMEN La obesidad es una enfermedad multifactorial definida como acumulación patológica de grasa. Su prevalencia ha aumentado enormemente en el mundo. Chile presenta una de las mayores prevalencias de obesidad de la OCDE. Su casuística simplificada comprende una diferencia sostenida entre gasto e ingesta de energía, manteniendo un delta positivo traducido en mayor acumulación de grasa. No obstante, la etiología completa de esta enfermedad comprende también factores psicológicos, genéticos, ambientales, etc. El ambiente juega un papel clave en la predisposición al consumo de alimentos, a la realización de ejercicio físico, incluso afectando la susceptibilidad genómica, exacerbando o disminuyendo la carga genética. Esta modificación de susceptibilidad genética por el ambiente se conoce como epigenética, que se refiere a una serie de modificaciones por "sobre" la genética que son altamente modificables por factores ambientales. Se ha descrito que algunas de estas modificaciones pueden heredarse de una generación a otra, lo que otorga otro nivel de complejidad al estudio de nuevas terapias complementarias para frenar la tendencia al sobrepeso. En la presente revisión se describe cuales son las modificaciones epigenéticas más frecuentes encontradas, su relación con obesidad y dieta, y finalmente como se relaciona con la transmisión transgeneracional de esta patología.

ABSTRACT Obesity is a multifactorial disease defined by a pathological accumulation of body fat. Its prevalence has increased greatly across the world. Chile has one of the highest prevalence of obesity among OCDE countries. It is caused by a sustained difference between energy expenditure and intake, keeping a positive delta, which drives fat accumulation. However, its etiology is comprised several factors: psychological, genetics, environmental, etc. The environment plays a key role in the predisposition towards food consumption, the adoption of exercise, and genetic susceptibility, increasing or decreasing the genetic load towards obesity. This modification of susceptibility is known as epigenetics, which refers to modifications "over" genetics, which are highly modifiable by environmental factors. Some of these modifications can be inherited from one generation to another, granting a higher complexity level regarding designing novel complementary therapies against obesity. Thus, the present review described which epigenetic modifications are related to obesity and different dietary patterns, and finally how epigenetic modifications can be related to transgenerational transmission of obesity.

A Review of the Potential of Chilean Native Berries in the Treatment of Obesity and its Related Features.

Obesity is a major worldwide health threat. It is characterized by an abnormal adipose tissue overgrowth together with increased monocytes infiltration, causing inflammation and oxidative stress, events associated with several illnesses. Investigations have focused on the benefits of native fruit consumption, claiming these to be natural sources of bioactive compounds with antioxidant and anti-inflammatory characteristics. It has been widely stated that berries are a source of the most antioxidant compounds, and, thus, seem highly promising to endure research efforts on these vegetal matrices. The present article describes botanical, chemical and biomedical features of the Chilean native berries, Aristotelia chilensis, Ugni molinae, and Berberis microphylla. This work aims to potentiate incoming research focused on the search for novel treatments for first-order diseases with these particular plant sources.

[High intensity interval training in teenagers]. / Efectividad de ejercicio físico intervalado de alta intensidad en las mejoras del fitness cardiovascular, muscular y composición corporal en adolescentes: una revisión.

This review analyzes the effects of high intensity interval training (HIIT) on muscle and cardiovascular fitness and body composition in teenagers. A search was carried out in international databases, finding 145 papers and selecting five for analysis. In all the reviewed manuscripts, peak oxygen uptake improved after HIIT. In the three manuscripts that measured muscle strength, it also increased. We conclude that HIIT improves muscle strength and cardiovascular fitness in school age children. A 12 weeks protocol with three 12-minute sessions per week would be ideal.

Nutritional and non-nutritional agents that stimulate white adipose tissue browning.

Obesity is a public health problem present in both developed and developing countries. The white adipose tissue (WAT) is the main deposit of lipids when there is an excess of energy. Its pathological growth is directly linked to the development of obesity and to a wide number of comorbidities, such as insulin-resistance, cardiovascular disease, among others. In this scenario, it becomes imperative to develop new approaches to the treatment and prevention of obesity and its comorbidities. It has been documented that the browning of WAT could be a suitable strategy to tackle the obesity epidemic that is developing worldwide. Currently there is an intense search for bioactive compounds with anti-obesity properties, which present the particular ability to generate thermogenesis in the brown adipose tissue (BAT) or beige. The present study provide recent information of the bioactive nutritional compounds capable of inducing thermogenesis and therefore capable of generate positive effects on health.

Efectividad de ejercicio físico intervalado de alta intensidad en las mejoras del fitness cardiovascular, muscular y composición corporal en adolescentes: una revisión / High intensity interval training in teenagers

This review analyzes the effects of high intensity interval training (HIIT) on muscle and cardiovascular fitness and body composition in teenagers. A search was carried out in international databases, finding 145 papers and selecting five for analysis. In all the reviewed manuscripts, peak oxygen uptake improved after HIIT. In the three manuscripts that measured muscle strength, it also increased. We conclude that HIIT improves muscle strength and cardiovascular fitness in school age children. A 12 weeks protocol with three 12-minute sessions per week would be ideal.