Dra. Mardones-Leiva, Lorena

Background: little information is availaible on the effect of fructose on bile lipids. The first stage in the formation of gallstones corresponds to biliary cholesterol crystallization, derived from the vesicular transporters. The aim of this study was to investigate the influence of consuming diets with different fructose concentrations on serum lipids and their implications on gallstones formation. Methods: BALB/c mice divided into a control group as well as groups were treated with different fructose concentrations (10 %, 30 %, 50 % or 70 %) for different periods (1, 2 or 5 months). Blood, liver and bile samples were obtained. In bile samples, cholesterol and phospholipids levels were analyzed, and cholesterol transporters (vesicles and micelles) were separated by gel filtration chromatography. Results: treated animals showed: 1) increases in body weight similar to the control group; 2) a significant increase in plasma triglycerides only at very high fructose concentrations; 3) a significant increase in total serum cholesterol in the treatment for 1 month; 4) no variations in HDL-cholesterol; 5) a significant increase in serum glucose only at very high fructose concentrations in the second month of treatment; 6) no differences in the plasma alanine-aminotransferase activity; 7) a significant increase in liver triglyceride levels only at very high fructose concentrations; 8) no change in biliary lipid concentrations or in micellar and vesicular phospholipids. Conclusion: changes in plasma, liver and bile lipids were only observed at very high fructose concentrations diets. We conclude that fructose apparently does not alter the gallstone formation process in our experimental model.

Introducción: La diabesidad se define como la coexistencia de obesidad y diabetes mellitus tipo 2 (DMT2). En Chile su prevalencia aún no ha sido definida. El objetivo de este estudio fue determinar la prevalencia de prediabesidad y diabesidad en adultos chilenos. Material y Método: Estudio transversal que incluyó 4.985 adultos mayores de 18 años de la Encuesta Nacional de Salud 2016-2017. El estado nutricional fue determinado por índice de masa corporal y DMT2 por una glicemia en ayuno ≥126 mg/dL o auto-reporte médico. Utilizando la combinación de estas dos variables, se definieron 6 fenotipos: normal sin diabetes, normo-diabetes, sobrepeso sin diabetes, prediabesidad, obesidad sin diabetes y diabesidad. La prevalencia de estos fenotipos se estudió según características sociodemográficas y estilos de vida. Resultados: La prevalencia de diabesidad, prediabesidad y normo-diabetes fue de 5,7%, 3,6% y 2,5%, respectivamente. Adicionalmente, la prevalencia de diabesidad fue mayor en mujeres, en personas con menos de 8 años de escolaridad y en aquellos con una edad de diagnóstico entre 45 y 46 años. Conclusión: El 9,3% de la población presentó prediabesidad o diabesidad, con una mayor proporción de los casos de diabesidad en mujeres y personas con bajo nivel de escolaridad. Considerando las proyecciones de aumento de obesidad y DMT2 en Chile, resulta urgente generar acciones y estrategias en esta materia, ya que una gran proporción de los casos de estas patologías pueden ser prevenibles.

Alternariol is a toxic metabolite of Alternaria fungi and studies have shown multiple potential pharmacological effects. To outline the anticancer effects and mechanisms of alternariol and its derivatives based on database reports, an updated search of PubMed/MedLine, ScienceDirect, Web of Science, and Scopus databases was performed with relevant keywords for published articles. The studies found to suggest that this mycotoxin and/or its derivatives have potential anticancer effects in many pharmacological preclinical test systems. Scientific reports indicate that alternariol and/or its derivatives exhibit anticancer through several pathways, including cytotoxic, reactive oxygen species leading to oxidative stress and mitochondrial dysfunction-linked cytotoxic effect, anti- inflammatory, cell cycle arrest, apoptotic cell death, genotoxic and mutagenic, anti-proliferative, autophagy, and estrogenic and clastogenic mechanisms. In light of these results, alternariol may be one of the hopeful chemotherapeutic agents.

Objective: To investigate the association between a lifestyle score and all-cause mortality in the Chilean population. Design: Prospective study. Settings: The score was based on seven modifiable behaviours: salt intake, fruit and vegetable intake, alcohol consumption, sleep duration, smoking, physical activity and sedentary behaviours. 1-point was assigned for each healthy recommendation. Points were summed to create an unweighted score from 0 (less healthy) to 7 (healthiest). According to their score, participants were then classified into: less healthy (0–2 points), moderately healthy (3–4 points) and the healthiest (5–7 points). Associations between the categories of lifestyle score and all-cause mortality were investigated using Cox proportional hazard models adjusted for confounders. Nonlinear associations were also investigated. Participants: 2706 participants from the Chilean National Health Survey 2009–2010. Results: After a median follow-up of 10·9 years, 286 (10·6 %) participants died. In the maximally adjusted model, and compared with the healthiest participants, those less healthy had 2·55 (95 % CI 1·75, 3·71) times higher mortality risk due to any cause. Similar trends were identified for the moderately healthy group. Moreover, there was a significant trend towards increasing the mortality risk when increasing unhealthy behaviours (hazard ratio model 3: 1·61 (95 % CI 1·34, 1·94)). There was no evidence of nonlinearity between the lifestyle score and all-cause mortality. Conclusion: Individuals in the less healthy lifestyle category had higher mortality risk than the healthiest group. Therefore, public health strategies should be implemented to promote adherence to a healthy lifestyle across the Chilean population.

Antecedentes. El receptor de melanocortina 4 (MC4R) participa en el control del apetito a nivel del sistema nervioso central, a través de la vía de la leptina-melanocortina. Se ha reportado asociación entre diferentes polimorfismos del gen MC4R y la obesidad; sin embargo, existen escasos estudios del polimorfismo de nucleótido simple (SNP) rs483145 de este gen. Objetivo. Investigar su prevalencia y asociación con marcadores de adiposidad en adultos chilenos. Métodos. La prevalencia del SNP rs483145, del gen MC4R, fue determinada en 259 participantes del estudio Genes, Ambiente, Diabetes y Obesidad (GENADIO) mediante reacción en cadena de la polimerasa (PCR) en tiempo real. La asociación del alelo de riesgo de MC4R (A) con marcadores de adiposidad (peso corporal, índice de masa corporal, porcentaje de masa grasa, perímetro de cadera, perímetro de cintura e índice cintura/cadera), se realizó mediante análisis de regresión lineal y fue ajustada por variables de confusión (sociodemográficas y de actividad física) mediante 3 modelos estadísticos. Resultados. Se determinó que la prevalencia del alelo de riesgo (A) del SNP rs483145 del gen MC4R es del 24,5% en la población adulta chilena incluida en este estudio, sin encontrar asociación con ninguno de los marcadores de adiposidad estudiados, tanto en modelos ajustados como sin ajustar.

Differentiated mammary epithelial cells are responsible for milk synthesis during lactation, supporting early postnatal life in mammals. These cells are found in the terminal alveoli of a secretory epithelium, which is surrounded by myoepithelial cells and a stroma rich in fatty tissue. The aim of this study was to explore the cell-specific expression of the glucose transporter GLUT8 in mammary gland and evaluate its functionality for glucose transport, in order to confirm its role in lactose synthesis. Our histological results revealed that GLUT8 is expressed in adipocytes and the epithelial and myoepithelial cells in mammary gland, with a predominant intracellular granular pattern. Colocalization studies of endogenous and green fluorescent protein fused GLUT8 revealed their expressions in lysosome and Golgi, respectively, with Pearson's coefficient correlations of 0.82 ± 0.05 and 0.68 ± 0.16. Functional studies of dileucine to dialanine mutant of GLUT8 showed a fructose-sensitive 2-deoxy glucose uptake at a rate of 83.3 pmoles/(min∗106 cells), 7 folds over empty vector, with a 60 ± 4 and 72 ± 6% decline in 2-deoxy glucose in the presence of 20 and 50 mM fructose, respectively. We concluded that functional GLUT8 is expressed in mammary gland, localizing in mammary epithelial and myoepithelial cells, and adipocytes. In lactation, GLUT8 is expressed mainly in luminal epithelial cells, at the compartments of the endomembrane system. It is necessary to explore the physiological/pathological functions of GLUT8 in mammary gland, including its role in lactation.

Introducción: La lactancia materna (LM) es un factor protector contra la obesidad infantil; sin embargo, los mecanismos a través de los cuales ejerce este efecto aún no están claros. El objetivo fue describir los mecanismos asociados al efecto protector que ejerce la lactancia materna contra la obesidad infantil. Métodos: Se utilizaron los buscadores PUBMED, SCOPUS, Cochrane Library y Scielo para desarrollar una revisión descriptiva de la evidencia científica. Las palabras clave fueron: lactancia materna, obesidad, mecanismo y dieta. Se revisaron artículos en español e inglés, desde 1977 hasta el 2020. Resultados: El efecto protector de la LM contra la obesidad infantil está dado por una combinación de varios mecanismos, se destaca su composición nutricional y el aporte de sustancias bioactivas, algunas de ellas reguladoras de la ingesta energética. Los lactantes que reciben LM por más tiempo seleccionan alimentos más saludables en etapa preescolar, independiente de factores sociodemográficos. También han sido descritos efectos en la adiposidad, el control del peso corporal y la ingesta energética mediante regulación de la programación epigenética y de la microbiota intestinal. Conclusión: La LM es un proceso único, que interacciona de forma compleja con factores del crecimiento y desarrollo de los lactantes y preescolares. Su rol protector contra la obesidad ha sido asociado a diversos mecanismos. Sin embargo, se requiere de nuevas investigaciones para comprender los alcances que puede presentar la LM en la etapa pediátrica y su rol en la prevención de la obesidad.

The study describes the current state of knowledge on nanotechnology and its utilization in medicine. The focus in this manuscript was on the properties, usage safety, and potentially valuable applications of chitosan-based nanomaterials. Chitosan nanoparticles have high importance in nanomedicine, biomedical engineering, discovery and development of new drugs. The manuscript reviewed the new studies regarding the use of chitosan-based nanoparticles for creating new release systems with improved bioavailability, increased specificity and sensitivity, and reduced pharmacological toxicity of drugs. Nowadays, effective cancer treatment is a global problem, and recent advances in nanomedicine are of great importance. Special attention was put on the application of chitosan nanoparticles in developing new system for anticancer drug delivery. Pre-clinical and clinical studies support the use of chitosan-based nanoparticles in nanomedicine. This manuscript overviews the last progresses regarding the utilization, stability, and bioavailability of drug nanoencapsulation with chitosan and their safety.

Type 2 diabetes Mellitus (T2DM) prevalence has significantly increased worldwide in recent years due to population age, obesity, and modern sedentary lifestyles. The projections estimate that 439 million people will be diabetic in 2030. T2DM is characterized by an impaired β-pancreatic cell function and insulin secretion, hyperglycemia and insulin resistance, and recently the epigenetic regulation of β-pancreatic cells differentiation has been underlined as being involved. It is currently known that several bioactive molecules, widely abundant in plants used as food or infusions, have a key role in histone modification and DNA methylation, and constituted potential epidrugs candidates against T2DM. In this sense, in this review the epigenetic mechanisms involved in T2DM and protein targets are reviewed, with special focus in studies addressing the potential use of phytochemicals as epidrugs that prevent and/or control T2DM in vivo and in vitro. As main findings, and although some controversial results have been found, bioactive molecules with epigenetic regulatory function, appear to be a potential replacement/complementary therapy of pharmacological hypoglycemic drugs, with minimal side effects. Indeed, natural epidrugs have shown to prevent or delay the T2DM development and the morbidity associated to dysfunction of blood vessels, eyes and kidneys due to sustained hyperglycemia in T2DM patients.

Background: Genetic variants within the FTO gene have been associated with increased adiposity and metabolic markers; however, there is limited evidence regarding the association of FTO gene variants with physical activity-related variables. The authors aimed to investigate the association of the rs17817449 single-nucleotide polymorphism of FTO with physical activity, sedentary time, and cardiorespiratory fitness in Chilean adults. Methods: A total of 409 participants from the GENADIO study were included and genotyped for the rs17817449 single-nucleotide polymorphism of FTO in this cross-sectional study. Physical activity and sedentary time were measured with ActiGraph accelerometers. Cardiorespiratory fitness was assessed using the Chester step test. The associations were assessed by using multivariate regression analyses. Results: No associations were found for FTO variant with physical activity levels and cardiorespiratory fitness. The risk allele (G) of the FTO was found to be associated with sedentary time in the minimally adjusted model (β = 19.7 min/d; 95% confidence interval, 4.0 to 35.5, per each copy of the risk allele; P = .006), but the association was no longer significant when body mass index was included as a confounder (P = .211). Conclusion: The rs17817449 single-nucleotide polymorphism of the FTO gene was not associated with the level of physical activity, cardiorespiratory fitness, and sedentary behaviors in Chilean adults.