Dr. Villagran-Orellana, Marcelo

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.

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.

Certain countries have the privilege of diverse ecosystems that allow access to wide food availability. This fact carries an intrinsic diversity in bioactive compounds such as phytochemicals, especially polyphenols. The aim of this review is to summarize the advances in polyphenols research which have been conducted in Chile, with a focus on polyphenol-rich foods and health-related outcomes. In the first part, several studies that have analyzed food sources rich in polyphenols are presented. This is followed by a description of in vitro and in vivo studies from Chile that have evaluated the polyphenol compounds of Chilean foods or their extracts along with their biological activity or health effects. Most polyphenol studies in our search have an in vitro experimental design where mainly protective activities are tested. The antioxidant effect is remarkable in all studies. As well as discussing the future direction of dietary assessment and the approach to biomarkers in this field, currently, additional emphasis and research investment are necessary to explore more native foods with an added value.

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.

GLUT1 is a facilitative glucose transporter that can transport oxidized vitamin C (i.e., dehydroascorbic acid) and complements the action of reduced vitamin C transporters. To identify the residues involved in human GLUT1’s transport of dehydroascorbic acid, we performed docking studies in the 5 Å grid of the glucose-binding cavity of GLUT1. The interactions of the bicyclic hemiacetal form of dehydroascorbic acid with GLUT1 through hydrogen bonds with the -OH group of C3 and C5 were less favorable than the interactions with the sugars transported by GLUT1. The eight most relevant residues in such interactions (i.e., F26, Q161, I164, Q282, Y292, and W412) were mutated to alanine to perform functional studies for dehydroascorbic acid and the glucose analog, 2-deoxiglucose, in Xenopus laevis oocytes. All the mutants decreased the uptake of both substrates to less than 50%. The partial effect of the N317A mutant in transporting dehydroascorbic acid was associated with a 30% decrease in the Vmax compared to the wildtype GLUT1. The results show that both substrates share the eight residues studied in GLUT1, albeit with a differential contribution of N317. Our work, combining docking with functional studies, marks the first to identify structural determinants of oxidized vitamin C’s transport via GLUT1.

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.

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.

Objective: To study the association of SLC16A11 gene variants with obesity and metabolic markers in nondiabetic Chilean adults. Materials and methods: This cross-sectional study included 263 nondiabetic adults. The genotype of the rs75493593 polymorphism of SLC16A11 gene was performed by real-time PCR. It’s association with adiposity markers (body weight, BMI, waist circumference and fat mass percentage), metabolic markers (glucose, insulin, HOMAIR, leptin, total cholesterol, LDLc, HDLc, triglycerides, ALT, GGT and hsCRP) and blood pressure was analyzed by linear regression. Results: The minor allele (T) of the SLC16A11 gene (rs75493593) has a frequency of 29.7% among Chileans. Risk genotypes (GT and TT) were associated with a significant 1.49 mU/l increase in plasmatic insulin for each copy of the minor allele (95% CI: 0.12, 2.87, p < 0.05). This association remained significant after adjusting for socio-demographic variables, physical activity and smoking (1.36 mU/l, 95% CI: 0.16, 2.58 p < 0.05), but was lost when BMI was included as a confounding factor. Higher BMI was also significantly associated with polymorphic genotypes in SLC16A11, independent of sociodemographic variables. Conclusion: The minor allele of the SLC16A11 gene (T) is highly prevalent among Chileans and is associated with increased insulin and BMI in nondiabetic individuals. These findings suggest that the genetic variant in SLC16A11 is not only associated with type 2 diabetes as previously shown in Mexicans, but is also related to early metabolic alterations in healthy subjects that may lead to type 2 diabetes.