Research Outputs

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Supercharging metabolic health with Lycium barbarum L.: A review of the therapeutic potential of this functional food for managing metabolic syndrome

2024, Dra. Mardones-Leiva, Lorena, Sharifi‐Rad, Javad, Quetglas‐Llabrés, Maria, Sureda, Antoni, Villagran, Marcelo, Sönmez-Gürer, Eda, Živković, Jelena, Ezzat, Shahira, Zayed, Ahmed, Gümüşok, Safa, Sibel Kılıç, Ceyda, Fasipe, Babatunde, Laher, Ismail, Martorell, Miquel

Metabolic syndrome (MetS) is a common disorder involving a cluster of metabolic abnormalities, such as abdominal obesity, hypertension, dyslipidemia, insulin resistance, and atherogenic profile. MetS is characterized by an increase in oxidative stress and a chronic proinflammatory state, which are directly related to the development and progression of this pathology. It has been seen how a healthy lifestyle and good dietary practices are key to improving the different metabolic parameters and, therefore, play a fundamental role in reducing the risk of developing diabetes. The present review focuses on the research evidence related to the therapeutic properties of Lycium barbarum L. in MetS gathered in the last years. Several preclinical studies suggest that L. barbarum extracts are a good dietary supplement for the prevention of cardiovascular diseases in people with MetS. This compound has been used for years in traditional Chinese medicine for the treatment of atrophic gastritis, problems related to the lungs, kidneys, and liver, and as a supplement for eye health. In addition, different in vitro and in vivo studies have been carried out that support the properties attributed to metabolites derived from L. barbarum, such as polysaccharides that have been shown diverse biological activities. In conclusion, L. barbarum extracts have multiple benefits to increase general well‐being and immune function. However, there are a limited number of studies related to effect of L. barbarum in MetS, but they demonstrated effectiveness in the treatment of obesity, diabetes mellitus type 2, and prevention of diabetes mellitus type 2 complication.

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ABSI obesity index and its association with type 2 diabetes mellitus in Chilean adults: a cross-sectional study of the ENS 2016-2017

2023, Dra. Mardones-Leiva, Lorena, Dra. Troncoso-Pantoja, Claudia, Parra-Soto, Solange, Lasserre-Laso, Nicole, Petermann-Rocha, Fanny, Martínez-Sanguinetti, María, Martorell, Miquel, Ramírez, Karina, Labraña, Ana, Nazar, Gabriela, Leiva-Ordoñez, Ana, Díaz-Martínez, Ximena, Celis-Morales, Carlos

Introducción: El nuevo índice de obesidad basado en el volumen corporal (ABSI), ha sido asociado con enfermedades crónicas no transmisibles y mortalidad, independiente de los valores del índice de masa corporal (IMC); sin embargo, se desconoce su asociación con diabetes mellitus tipo 2 (DMT2) en población chilena. Objetivo: determinar la asociación entre ABSI con glicemia, hemoglobina glicosilada (HbAc1) y DMT2 en población adulta chilena. Materiales y métodos: Estudio transversal, incluyó a 4.874 participantes (edad media 43,3 años, 50,9% mujeres) de la Encuesta Nacional de Salud 2016-2017. ABSI fue calculado según la fórmula propuesta (basado en circunferencia de cintura, IMC y estatura. La Regresión de Poisson fue utilizada para investigar la asociación entre ABSI con DMT2 y regresión lineal para glicemia y HbAc1. Los análisis se ajustaron según factores sociodemográficos, de estilos de vida e IMC. Resultados: ABSI fue positivamente asociado con glicemia (p<0,001), HbA1c (p<0,001) y DMT2 (p<0,001). En el modelo más ajustado, por cada 0.025 unidad de aumento de ABSI, la glicemia aumentó en 1,78 mg/dL (95% IC: 1,21; 2,35) y la HbAc1en un 0,92% (95% IC: 0,49; 1,35). En cuanto a DMT2, la razón de prevalencia fue de 1,14 (95% IC: 1,09; 1,20), independiente de factores sociodemográficos, estilos de vida e IMC. Conclusiones: ABSI se asoció de forma lineal con una mayor probabilidad de padecer DMT2, mayores niveles de glicemia y HbA1c en adultos chilenos. En este contexto, ABSI podría ser un índice complementario, independiente del IMC, para evaluar el riesgo de alteraciones metabólicas asociadas a obesidad.

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El polimorfismo rs483145 del gen MC4R no se asocia con obesidad en población chilena: Resultados del estudio GENADIO

2022, Dra. Mardones-Leiva, Lorena, Dr. Villagrán-Orellana, Marcelo, Parra-Valencia, Esteban, Petermann-Rocha, Fanny, Martínez-Sanguinetti, María, Leiva-Ordoñez, Ana María, Lasserre-Laso, Nicole, Martorell, Miquel, Ulloa, Natalia, Sanhueza, Eduardo, Pérez-Bravo, Francisco, Celis-Morales, Carlos

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.

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Cell-specific expression of functional glucose transporter 8 in mammary gland

2021, Dra. Mardones-Leiva, Lorena, Muñoz, Katia, Dr. Villagrán-Orellana, Marcelo

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.

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Effect of various dietary fructose concentrations on the gallstone formation process in mice

2024, Dra. Mardones-Leiva, Lorena, Dr. Villagrán-Orellana, Marcelo, Mg. Muñoz-Roa, Mirna, Del Pozo-Iribarren, Reginald, Muñoz-Parra, Katia, Troncoso-Ramírez, Luciano, Mellado-Arias, Maximiliano

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.

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An updated overview of anticancer effects of alternariol and its derivatives: Underlying molecular mechanisms

2023, Torequl-Islam, Muhammad, Martorell, Miquel, González-Contreras, Carlos, Dr. Villagrán-Orellana, Marcelo, Dra. Mardones-Leiva, Lorena, Tynybekov, Bekzat, Oana-Docea, Anca, Ahmad Faizal Abdull Razis, Modu, Babagana, Calina, Daniela, Sharifi-Rad,Javad

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.

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El complejo escenario molecular gatillado por el ejercicio físico agudo

2022, Dra. Mardones-Leiva, Lorena, Celis Morales, Carlos

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Prevalencia de prediabesidad y diabesidad en Chile: Resultados de la Encuesta Nacional de Salud 2016-2017

2024, Dra. Mardones-Leiva, Lorena, Dr. Villagrán-Orellana, Marcelo, Martorell, Miquel, Opazo, Makarena, Ramírez-Alarcón, Karina, Labraña, Ana, Nazar, Gabriela, Concha-Cisternas, Yeny, Díaz-Toro, Felipe, Lanuza, Fabian, Celis-Morales, Carlos, Petermann-Rocha, Fanny

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.

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Association between a lifestyle score and all-cause mortality: A prospective analysis of the Chilean National Health Survey 2009–2010

2023, Dra. Mardones-Leiva, Lorena, Dra. Troncoso-Pantoja, Claudia, Dr. Villagrán-Orellana, Marcelo, Petermann-Rocha, Fanny, Diaz-Toro, Felipe, Martínez-Sanguinetti, María Adela, Leiva-Ordoñez, Ana, Nazar, Gabriela, Concha-Cisternas, Yeny, Díaz Martínez, Ximena, Lanuza, Fabian, Carrasco-Marín, Fernanda, Martorell, Miquel, Ramírez-Alarcón, Karina, Labraña, Ana María, Parra-Soto, Solange, Lasserre-Laso, Nicole, Cigarroa, Igor, Vásquez-Gómez, Jaime, Celis-Morales, Carlos

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.

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Association of adiposity and diabetes mellitus type 2 by education level in the Chilean population

2021, Dra. Mardones-Leiva, Lorena, Dr. Matus-Castillo, Carlos, Dra. Troncoso-Pantoja, Claudia, Parra-Soto, Solange, Leiva-Ordoñez, Ana, Petermann-Rocha, Fanny, Martínez-Sanguinetti, María, Martorell, Miquel, Ulloa, Natalia, Concha-Cisternas, Yeny, Cigarroa, Igor, Villagrán, Marcelo, Laserre-Laso, Nicole, Celis-Morales, Carlos

Background: Adiposity and education are two independent risk factors for type 2 diabetes (T2D). However, there is limited evidence whether both education and adiposity are associated with T2D in an additive manner in the Chilean population. Aim: To investigate the joint association between adiposity and education with T2D in the Chilean adult population. Material and Methods: Analysis of data of the Chilean National Health Survey 2016-2017, which included 5,033 participants with a mean age of 43 years, (51% women). Poisson regression analyses with robust standard error were used to investigate the joint association of the education level and general and central adiposity with T2D. The results were reported as Prevalence Ratio and their 95% confidence intervals (PR, 95% CI). Results: Obesity was associated with a higher probability of having T2D in men than in women, however central adiposity was associated with a higher probability of having T2D in women than in men. Compared with men who had higher education (> 12 years) and had normal body weight, those with the same educational level and who were obese had 2.3-times higher probability of having T2D (PR: 2.35 [95% CI: 1.02; 5.39]). For women, having a low education and being obese was associated with 4.4-times higher probability of having T2D compared to those with higher education and normal body mass index (BMI) (PR: 4.47 [95% IC: 2.12; 9.24]). Similar results were observed when waist circumference was used as a marker of obesity rather than BMI. Conclusions: Women and men with higher BMI and low education had a higher risk of T2D. However, this risk was higher in women than in men.