Dra. Mardones-Leiva, Lorena

La obesidad es una enfermedad inflamatoria, crónica, recurrente, progresiva y de etiología multifactorial, que afecta a más 650 millones de personas en el mundo. La carga física, emocional y económica que genera la obesidad no solo guarda relación con sus manifestaciones clínicas, sino también por su impacto a nivel sistémico y a largo plazo. En Chile, el crecimiento económico, la urbanización y la globalización han modificado profundamente el modo de vivir de la población lo que ha favorecido un ambiente obesogénico. Sin embargo, ¿qué factores han repercutido en el desarrollo de obesidad en Chile? ¿cuál ha sido el rol de cada uno de estos factores en el aumento de la prevalencia de esta patología? En la parte 1 de esta revisión discutiremos los principales factores no modificables que han repercutido en su desarrollo, desde la transición epidemiológica que vivió el país en la década de los 70, hasta las patologías endocrinas relacionadas.

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 prevention in a Mendelian randomized study. In conclusion, the role of vitamin C in the prevention and treatment of cancer is still an ongoing area of research. It is necessary that new phase II and III clinical trials be performed to collect stronger evidence of the therapeutic role of vitamin C in cancer.

Los factores del estilo de vida podrían promover un envejecimiento saludable. Objetivo: Investigar la asociación entre la actividad física (PA), comportamiento sedentario y deterioro cognitivo en chilenos mayores adultos. Material y Métodos: Se incluyeron 1.390 participantes de la Encuesta Nacional de Salud (2009-2010). El Mini-mental El examen estatal se utilizó para diagnosticar el deterioro cognitivo. La actividad física y el comportamiento sedentario fueron evaluados con Cuestionario Global de Actividad Física (GPAQ). Regresión Logística se realizó para investigar las asociaciones. Resultados: Comparados con adultos mayores con niveles más bajos de PA (< 48 min/día), aquellos con niveles medios (48-248 min/día) y más altos (>248 min/día) de PA tuvieron menores probabilidades de deterioro cognitivo (Odds ratio (OR): 0,57 [95% IC: 0,32; 0,83], p < 0,01, respectivamente). Los participantes que informaron que pasaban más de 8 horas al día sentados tenían una alta probabilidad de deterioro cognitivo en comparación con aquellos que pasaban < 4 horas/ día (OR: 3,70 [IC 95%: 1,37; 6,03], p = 0,01). Conclusiones: Tanto la PA como el comportamiento sedentario se asociaron independientemente con el deterioro cognitivo independiente de los principales factores de confusión en adultos mayores chilenos.

Background: Numerous studies have identified the role of Fat-mass-associated-gene (FTO) in the development of obesity. Aim: To investigate the association of FTO gene with adiposity markers in Chilean adults. Material and Methods: 409 participants were included in this cross-sectional study. The association between FTO (rs9939609) genotype and adiposity markers was determined using linear regression analyses. Adiposity markers included were: body weight, body mass index, fat mass, waist circumference, hip circumference and waist/hip ratio. Results: A fully adjusted model showed a significant association between FTO genotype and body weight (2.16 kg per each extra copy of the risk allele [95% confidence intervals (CI): 0.45 to 3.87], p = 0.014), body mass index (0.61 kg.m-2 [95% CI: 0.12 to 1.20], p = 0.050) and fat mass (1.14% [95% CI: 0.39 to 1.89], p = 0.010). The greater magnitude of association was found between the FTO gene and fat mass when the outcomes were standardized to z-score. Conclusions: This study confirms an association between the FTO gene and adiposity markers in Chilean adults, which is independent of major confounding factors.

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 %. One quartile increment in sugar intake was associated with 1.50 kg [95% confidence interval (CI): 0.49; 2.50] higher body weight, 0.34 kg/m2 [95% CI: 0.01; 0.69] higher BMI, 1.23 cm [95% CI: 0.11; 2.34] higher WC, 1.39 cm [95% CI: 0.28; 2.50] higher HC and 0.02 the waist-to-hip ratio [95% C: 0.01; 0.02]. Conclusions: Total sugar intake was associated with higher adiposity levels in these Chilean adults.

Actualmente los edulcorantes no nutritivos (ENN) son ampliamente usados para endulzar los alimentos en reemplazo de los azúcares simples, con la ventaja de no aportar energía. A pesar de que en general no presentan efectos tóxicos, los estudios epidemiológicos no han podido evidenciar que su uso contribuya a mejorar la pérdida de peso, sino por el contrario, han revelado que los ENN pueden inducir alteraciones metabólicas como intolerancia a la glucosa. Estudios in vivo e in vitro han mostrado que muchos ENN activan a receptores del sabor dulce no sólo en los botones gustativos, sino que también en los receptores presentes en tejidos como el adiposo y pancreático, interfiriendo con su función normal. Además, el consumo ENN se ha asociado a alteraciones de la composición de la microbiota intestinal que conducen a una respuesta inflamatoria de bajo grado. La nueva evidencia disponible sobre los ENN hace necesario evaluar el uso cada vez más intenso de los ENN en Chile. Debido a que el gusto exacerbado por el sabor dulce que cultivamos desde la infancia es un potente catalizador del uso de ENN, proponemos que una oportuna educación del sentido del gusto puede contribuir a mejorar las elecciones alimentarias.

The liver has an extraordinary regenerative capacity in response to partial hepatectomy (PHx), which develops with neither tissue inflammation response nor alterations in the whole organism. This process is highly coordinated and it has been associated with changes in glutathione (GSH) metabolism. However, there are no reports indicating ascorbic acid (AA) levels after partial hepatectomy. AA and GSH act integrally as an antioxidant system that protects cells and tissues from oxidative damage and imbalance observed in a variety of diseases that affect the liver. Although rat hepatocytes are able to synthesize AA and GSH, which are the providers of AA for the whole organism, they also acquire AA from extracellular sources through the sodiumcoupled ascorbic acid transporter-1 (SVCT1). Here, we show that hepatocytes from rat livers subjected to PHx increase their GSH and AA levels from 1 to 7 days post hepatectomy, whose peaks precede the peak in cellproliferation observed at 3 days post-hepatectomy. The increase in both antioxidants was associated with higher expression of the enzymes involved in their synthesis, such as the modifier subunit of enzyme glutamine cysteine ligase (GCLM), glutathione synthetase (GS), gulonolactonase (GLN) and gulonolactone oxidase (GULO). Importantly, rat hepatocytes, that normally exhibit kinetic evidence indicating only SVCT1-mediated transport of AA, lost more than 90% of their capacity to transport it at day 1 after PHx without evidence of recovery at day 7. This observation was in agreement with loss of SVCT1 protein expression, which was undetectable in hepatocytes as early as 2 h after PHx, with partial recovery at day 7, when the regenerated liver weight returns to normal. We conclude that after PHx, rat hepatocytes enhance their antioxidant capacity by increasing GSH and AA levels prior to the proliferative peak. GSH and AA are increased by de novo synthesis, however paradoxically hepatocytes from rat subjected to PHx also suppress their capacity to acquire AA from extracellular sources through SVCT1.

Background: Type 2 diabetes etiology has a strong genetic component. More than 20 genetic variants have been associated with diabetes and other metabolic markers. However, the polymorphism rs7903146 of the TCF7L2 gene has shown the strongest association. Aim: To investigate the association of TCF7L2 (rs7903146) genotype with adiposity and metabolic markers in the Chilean adult population. Material and Methods: The association of TCF7L2 (rs7093146) with adiposity and metabolic markers was studied in 301 participants. The outcomes of the study were adiposity markers (body weight, body mass index (BMI), fat mass and waist circumference) and metabolic markers (blood glucose, insulin, HOMA-IR, lipid profile, high sensitivity C-reactive protein (CRP), alanine aminotransferase (ALT), gamma glutamyl transpeptidase (GGT) and leptin). Results: There was an association between the polymorphism TCF7L2 genotype and fasting blood glucose. The latter increased by 4.86 mg/dl per each copy of the risk allele [(95% confidence intervals (CI): 0.48; 9.24), p = 0.03] in the unadjusted adjusted model. However, this association was slightly attenuated in the fully adjusted model [4.38 mg/dl (95% IC: 0.16; 8.60), p = 0.04)]. There were no associations between the TCF7L2 genotype and any other metabolic or adiposity outcome. Conclusions: These findings confirm the association between the TCF7L2 (rs7903146) and fasting glucose in the Chilean population. However, further studies are needed to confirm the association between the TCF7L2 and diabetes risk in the Chilean population.

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.