Papers by Marcelo Villagrán
Children
Children carrying the minor allele ‘A’ at the fat mass and obesity-associated protein (FTO) gene ... more Children carrying the minor allele ‘A’ at the fat mass and obesity-associated protein (FTO) gene have higher obesity prevalence. We examined the link between FTO rs9939609 polymorphism and plasma adiponectin and the mediating role of body adiposity, in a cross-sectional study comprising 323 children aged 6–11 years. Adiponectin and FTO genotypes were assessed using a commercial kit and a real-time polymerase chain reaction with high-resolution melting analysis, respectively. Body adiposity included body mass index z-score, body fat percentage and waist-to-hip ratio. To investigate adiponectin (outcome) associations with FTO and adiposity, linear regressions were implemented in additive models and across genotype categories, adjusting for sex, age and Tanner’s stage. Using mediation analysis, we determined the proportion of the association adiponectin-FTO mediated by body adiposity. Lower adiponectin concentrations were associated with one additional risk allele (βadditive = −0.075 l...
Molecules
GLUT1 is a facilitative glucose transporter that can transport oxidized vitamin C (i.e., dehydroa... more 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 ...
Biochemical and Biophysical Research Communications
Differentiated mammary epithelial cells are responsible for milk synthesis during lactation, supp... more 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.
Archives of Endocrinology and Metabolism
Objective: To study the association of SLC16A11 gene variants with obesity and metabolic markers ... more 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, HOMA IR , 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.
Endocrinología, Diabetes y Nutrición (English ed.)
Antioxidants, 2021
Vitamin C is a water-soluble antioxidant associated with the prevention of the common cold and is... more Vitamin C is a water-soluble antioxidant associated with the prevention of the common cold and is also a cofactor of hydrolases that participate in the synthesis of collagen and catecholamines, and in the regulation of gene expression. In cancer, vitamin C is associated with prevention, progression, and treatment, due to its general properties or its role as a pro-oxidant at high concentration. This review explores the role of vitamin C in cancer clinical trials and the aspects to consider in future studies, such as plasmatic vitamin C and metabolite excretion recording, and metabolism and transport of vitamin C into cancer cells. The reviewed studies show that vitamin C intake from natural sources can prevent the development of pulmonary and breast cancer, and that vitamin C synergizes with gemcitabine and erlotinib in pancreatic cancer. In vitro assays reveal that vitamin C synergizes with DNA-methyl transferase inhibitors. However, vitamin C was not associated with cancer prevent...
Revista chilena de nutrición, 2021
Lactancia materna y su asociación con obesidad: Mecanismos que podrían explicar el rol protector ... more Lactancia materna y su asociación con obesidad: Mecanismos que podrían explicar el rol protector en la infancia Breastfeeding and its association with obesity: Mechanisms that might explain its protective role during childhood
Endocrinología, Diabetes y Nutrición, 2021
INTRODUCTION The melanocortin receptor 4 (MC4R) participates in the control of appetite at the le... more INTRODUCTION The melanocortin receptor 4 (MC4R) participates in the control of appetite at the level of the central nervous system, through the leptin-melanocortin pathway. An association between different polymorphisms of the MC4R gene and obesity has been reported. However, there are few studies of the rs483145 single nucleotide polymorphism (SNP) of this gene. OBJECTIVE To investigate its prevalence and association with adiposity markers in Chilean adults. METHODS The prevalence of SNP rs483145, of the MC4R gene, was determined in 259 participants of the GENADIO study (genes, environment, diabetes and obesity) by means of real-time polymerase chain reaction (PCR). The association between the risk allele of MC4R (A) and adiposity markers (body weight, body mass index, fat mass percentage, hip circumference, waist circumference, waist-to-hip ratio) was performed by linear regression analysis and adjusted for confusion variables (socio-demographic and physic activity) using three statistical models. RESULTS It was determined that the prevalence of the risk allele (A) of the SNP rs483145 of the MC4R gene is 24.5% in the Chilean adult population included in this study, without finding an association with any of the adiposity markers studied, both in adjusted and unadjusted models. CONCLUSION The presence of the risk allele of SNP rs483145 of the MC4R gene is not associated with adiposity markers in the Chilean adult population studied. New studies with a bigger sample size will be necessary to confirm these results.
ARS MEDICA Revista de Ciencias Médicas, 2021
Los suplementos deportivos que se etiquetan como ergogénicos son muchos, pero pocos son los que r... more Los suplementos deportivos que se etiquetan como ergogénicos son muchos, pero pocos son los que realmente han demostrado su efectividad como tal. Actualmente, su uso se ha masificado, tanto por falta de regulación en uso y venta, así como por su utilización en la población general, y no sólo en deportistas de alto rendimiento. Frente a estas limitantes ¿cuál es la efectividad de estos productos más allá de la moda? En esta comunicación breve se abordan algunos de los suplementos y plantas más utilizados como ergogénicos; no obstante, es necesario tener precaución al momento de generalizar los resultados obtenidos por algunos ergogénicos, ya que su efecto podría ser secundario y/o estar condicionado por otros factores.
Frontiers in Endocrinology, 2021
Type 2 diabetes Mellitus (T2DM) prevalence has significantly increased worldwide in recent years ... more 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 co...
Revista médica de Chile, 2018
Background: Fat-mass-associated-gene (FTO) is associated with higher energy intake and specific f... more Background: Fat-mass-associated-gene (FTO) is associated with higher energy intake and specific food preferences. Aim: To investigate the association of the FTO genotype with energy intake, macronutrient and alcohol consumption. Material and methods: Four hundred and nine participants of the GENADIO (Genes, Environment, Diabetes and Obesity) study were included. Energy intake, macronutrient and alcohol consumption were the outcomes of interest. The association of FTO (rs9939609) genotype with these outcomes was investigated using linear regression analyses, adjusting for confounding variables. Results: After adjusting for socio-demographic factors, being a carrier of the risk allele for the FTO gene was associated with a higher energy intake (173 kcal per each extra copy of the risk variant [95% confidence intervals (CI): 45; 301] (P=0.008). After adjusting for lifestyle factors and body mass index, the association was slightly attenuated but remained significant (144 kcal [95% CI: ...
espanolEl humo de tabaco causa dano oxidativo directamente por efecto de sus oxidantes o indirect... more espanolEl humo de tabaco causa dano oxidativo directamente por efecto de sus oxidantes o indirectamente por la induccion de la produccion de oxidantes endogenos y/o inactivacion de antioxidantes. El efecto oxidativo del humo de tabaco depende de varias variables: dosis, tiempo de exposicion, tejido o tipo cleular y estado antioxidante. En un intento de simplificar este complejo escenario, examinamos el efecto de un extracto soluble de humo de tabaco en la actividad de tres enzimas antioxidantes en estado purificado y en plasma humano (catalasa, glutation peroxidasa and superoxido dismutasa). Nuestro resultados revelan que catalasa y glutation peroxidasa fueron inhibidas con un IC50 de 18 y 80 equivalentes de fumador (unidades arbirtarias), respectivamente; mientras que superoxido dismutasa no fue afectada. Encontramos un efecto similar del extracto soluble de humo de tabaco en las enzimas antioxidantes plasmaticas, donde catalasa fue mas inhibida que superoxido dismutasa y glutation...
Gerokomos, 2020
Asociación entre la velocidad de marcha y el riesgo de deterioro cognitivo en personas mayores qu... more Asociación entre la velocidad de marcha y el riesgo de deterioro cognitivo en personas mayores que viven en la comunidad Association between self-reported walking pace and cognitive impairment in older adults no institutionalized in Chile RESUMEN Objetivos: Determinar si la velocidad de marcha lenta se asocia a un mayor riesgo de deterioro cognitivo en personas mayores de 60 años, sanas, que viven en la comunidad, e investigar si esta asociación es modificable según niveles de actividad física y tiempo que permanecen sentados. Métodos: Estudio correlacional, transversal y retrospectivo. Se incluyeron 1082 personas mayores de 60 años de la Encuesta Nacional de Salud (ENS) 2009-2010 de Chile. La velocidad de la marcha (normal o lenta) fue autorreportada y el riesgo de deterioro cognitivo se evaluó con el cuestionario Mini-Mental State Examination. Las variables sociodemográficas y de estilos de vida se obtuvieron mediante la aplicación de cuestionarios validados en la ENS 2009-2010. Adicionalmente se evaluó el estado nutricional a través del índice de masa corporal. Resultados: Las personas mayores que presentaban una menor velocidad de marcha evidenciaron un mayor riesgo de presentar deterioro cognitivo en comparación con aquellos que caminan a velocidad de paso normal (OR:1,62 [IC 95%:1,06;2,54], p = 0,036). Esta asociación fue independiente de factores sociodemográficos, obesidad, tiempo sedente, actividad física y estilos de vida. Conclusión: Las personas mayores que reportaron caminar a un paso más lento que sus pares de la misma edad presentan un mayor riesgo de deterioro en comparación con aquellos que tienen una velocidad de la marcha normal.
Nutrition, 2020
Is waist-to-height ratio a better predictor of hypertension and type 2 diabetes than body mass in... more Is waist-to-height ratio a better predictor of hypertension and type 2 diabetes than body mass index and waist circumference in the Chilean population? Nutrition, 79, 110932.
Revista Española de Nutrición Humana y Dietética, 2021
Introduction: La esperanza de vida está aumentando en todo el mundo, así como la diabetes tipo 2 ... more Introduction: La esperanza de vida está aumentando en todo el mundo, así como la diabetes tipo 2 (DM2). Estudios poblacionales han demostrado que la duración de la DM2 se ha asociado con el deterioro cognitivo. Sin embargo, a pesar de la alta prevalencia de DM2 y deterioro cognitivo en Chile, aún no se ha investigado la asociación entre años con DM2 y la sospecha de deterioro cognitivo. El objetivo del estudio fue investigar la asociación entre la duración de la diabetes mellitus 2 (DM2) y la sospecha de deterioro cognitivo en personas mayores chilenas. Métodos: Participaron 1.040 personas ≥60 años de la Encuesta Nacional de Salud de Chile (2009-2010). El deterioro cognitivo se evaluó mediante el Mini Examen del Estado Mental abreviado (MMSE). El número de años con DM2 fue categorizado en cuatro grupos. Para valorar la asociación entre MMSE alterado y el número de años con DM2, se utilizó una regresión de Poisson, ajustados a posibles factores de confusión sociodemograficos, de est...
Journal of Physical Activity and Health, 2021
Background: Genetic variants within the FTO gene have been associated with increased adiposity an... more 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 a...
Revista médica de Chile, 2020
del grupo de investigación elhoc. Association between cognitive impairment and depression in Chil... more del grupo de investigación elhoc. Association between cognitive impairment and depression in Chilean older adults Background: Depression has been previously associated with cognitive impairment in high income country populations. However, its association in the Chilean population has not been investigated. Aim: To investigate the association between depression and cognitive impairment. Material and Methods: Data from 1384 Chilean adults aged > 60 years, participating in the National Health Survey 2009-2010 was analyzed. Cognitive impairment was assessed using the Mini Mental Examination score. The medical diagnosis of depression was self-reported. The association between depression and cognitive impairment was assessed using a logistic regression. Results: Depression was positively associated with cognitive impairment. However, the magnitude of the association was higher in men (Odds ratio (OR) = 4.02 [95% confidence intervals (CI): 1.44; 6.61], p < 0.01]) than in women (OR = 2.23 [95%CI: 1.03; 3.43], p = 0.04). Older adults who were diagnosed for the first time with depression after 65 years of age, showed a stronger association with cognitive impairment (OR = 6.65 [95% CI: 2.39; 10.9], p < 0.01) than those diagnosed before 55 years. Conclusions: Our study confirms the association between depression and cognitive impairment. Further research is needed to elucidate the nature and potential mechanisms that link depression with cognitive impairment.
Revista médica de Chile, 2020
Total sugar consumption and its association with obesity in Chilean adults Background: Sugar inta... more Total sugar consumption and its association with obesity in Chilean adults Background: Sugar intake is a risk factor for the development of obesity. Aim: To investigate the association between total sugar intake and obesity markers in Chilean adults. Material and Methods: This cross-sectional study included 396 participants of the GENADIO study. Anthropometric measurements (body weight, body mass index (BMI), waist circumference (WC), hip circumference (HC), waist-to-hip ratio, and % body fat) were measured through standardized protocols. Total sugar intake was determined from a 7-days weighted food daily. Sugar intake expressed in g/day was categorized into quartiles. Results: Higher sugar intake was associated with a higher BMI, WC and HC but not with body fat %.
Revista chilena de nutrición, 2020
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Papers by Marcelo Villagrán