Dietary regulation of VEGFb gene expression is related to its promoter DNA methylation levels

Motivación: Recientemente se ha descrito la implicación del factor de crecimiento del endotelio vascular B (VEGFb) en la absorción de los ácidos grasos (AGs) en los tejidos y su relación con el desarrollo de diferentes enfermedades metabólicas tal como la obesidad y la diabetes tipo 2. El objetivo de este estudio es investigar el efecto de la composición de los AGs de la dieta en la regulación de la expresión génica del VEGFb en los tejidos adiposos de rata, y si este efecto está relacionado mediante modificación por metilación del DNA en el promotor del VEGFb. De esta forma la modificación de la dieta puede ser una nueva estrategia para modular la acumulación patológica de los lípidos en la obesidad o en la diabetes. Métodos: A cada grupo de ratas fue asignado una de tres diferentes dietas isoenergéticas, cada una con una concentración diferente de AGs saturados, mono y poliinsaturados (dieta de aceite de coco, aceite de oliva y de girasol). Los animales fueron alimentados durante un mes. Las muestras de tejido adiposo visceral (VAT) y subcutáneo (SAT) se tomaron inmediatamente para estudios de metilación y  expresión génica. También de estos tejidos se tomaron mediciones de la composición de los AGs de los triglicéridos y la acumulación total de los tejidos adiposos. Resultados: Ni los pesos de los animales ni de los depósitos adiposos ni la acumulación lípidica del tejido cambiaban con las dietas. La composición en AGs de ambos tejidos fue significativamente diferente en función de la dieta consumida(p <0,0001 para todos los AGs estudiados). El nivel de expresión del gen VEGFb se correlaciona directamente con la acumulación de lípidos de cada tejido y con la composición de AGs del tejido. En ambos tejidos, los niveles de expresión génica del VEGFb y de metilación del promotor fueron diferentes con respecto a la dieta consumida, estando la expresión génica y los niveles de metilación del promotor del VEGFb inversamente correlacionados. Los valores más altos de expresión génica, y los más bajos de metilación del promotor, se encontraron en las ratas alimentadas con la dieta rica en aceite de coco. Conclusiones: La expresión del gen Vegfb en el tejido adiposo se asocia con el aumento en la acumulación de grasa. El estudio presentado muestra que la expresión génica del Vegfb está regulada por los AGs de la dieta, y esta regulación está relacionada con el nivel de metilación de la región promotora del Vegfb

Antibodies Against β2-Glycoprotein I Complexed With an Oxidised Lipoprotein Relate to Intima Thickening of Carotid Arteries in Primary Antiphospholipid Syndrome

To explore whether antibodies against β2-glycoprotein I (β2GPI) complexed to 7-ketocholesteryl-9-carboxynonanoate (oxLig-1) and to oxidised low-density lipoproteins (oxLDL) relate to paraoxonase activity (PONa) and/or intima media thickness (IMT) of carotid arteries in primary antiphospholipid syndrome (PAPS). As many as 29 thrombotic patients with PAPS, 10 subjects with idiopathic antiphospholipid antibodies (aPL) without thrombosis, 17 thrombotic patients with inherited thrombophilia and 23 healthy controls were investigated. The following were measured in all participants: β2GPI−oxLDL complexes, IgG anti-β2GPI−oxLig-1, IgG anti-β2GPI−oxLDL antibodies (ELISA), PONa, (para-nitrophenol method), IMT of common carotid (CC) artery, carotid bifurcation (B), internal carotid (IC) by high resolution sonography. β2GPI−oxLDL complex was highest in the control group (p < 0.01), whereas, IgG anti-β2GPI−oxLig1 and IgG anti-β2GPI−oxLDL were highest in PAPS (p < 0.0001). In healthy controls, β2GPI−oxLDL complexes positively correlated to IMT of the IC (p = 0.007) and negatively to PONa after correction for age (p < 0.03). PONa inversely correlated with age (p = 0.008). In PAPS, IgG anti-2GPI−oxLig-1 independently predicted PONa (p = 0.02) and IMT of B (p = 0.003), CC, (p = 0.03) and of IC (p = 0.04). In PAPS, PONa inversely correlated to the IMT of B, CC and IC (p = 0.01, 0.02 and 0.003, respectively). IgG anti-2GPI−oxLig-1 may be involved in PAPS related atherogenesis via decreased PON activity

DNA multigene characterization of Fasciola hepatica and Lymnaea neotropica and its fascioliasis transmission capacity in Uruguay, with historical correlation, human report review and infection risk analysis

Fascioliasis is a highly pathogenic zoonotic disease emerging in recent decades, in part due to the effects of climate and global changes. South America is the continent presenting more numerous human fascioliasis endemic areas and the highest Fasciola hepatica infection prevalences and intensities known in humans. These serious public health scenarios appear mainly linked to altitude areas in Andean countries, whereas lowland areas of non-Andean countries, such as Uruguay, only show sporadic human cases or outbreaks. To understand this difference, we characterized F. hepatica from cattle and horses and lymnaeids of Uruguay by sequencing of ribosomal DNA ITS-2 and ITS-1 spacers and mitochondrial DNA cox1, nad1 and 16S genes. Results indicate that vectors belong to Lymnaea neotropica instead of to Lymnaea viator, as always reported from Uruguay. Our correlation of fasciolid and lymnaeid haplotypes with historical data on the introduction and spread of livestock species into Uruguay allow to understand the molecular diversity detected. We study the life cycle and transmission features of F. hepatica by L. neotropica of Uruguay under standardized experimental conditions to enable a comparison with the transmission capacity of F. hepatica by Galba truncatula at very high altitude in Bolivia. Results demonstrate that although L. neotropica is a highly efficient vector in the lowlands, its transmission capacity is markedly lower than that of G. truncatula in the highlands. On this baseline, we review the human fascioliasis cases reported in Uruguay and analyze the present and future risk of human infection in front of future climate change estimations

Cardiovascular disease, chronic kidney disease, and diabetes mortality burden of cardiometabolic risk factors from 1980 to 2010: a comparative risk assessment

Background High blood pressure, blood glucose, serum cholesterol, and BMI are risk factors for cardiovascular diseases and some of these factors also increase the risk of chronic kidney disease and diabetes. We estimated mortality from cardiovascular diseases, chronic kidney disease, and diabetes that was attributable to these four cardiometabolic risk factors for all countries and regions from 1980 to 2010. Methods We used data for exposure to risk factors by country, age group, and sex from pooled analyses of populationbased health surveys. We obtained relative risks for the eff ects of risk factors on cause-specifi c mortality from metaanalyses of large prospective studies. We calculated the population attributable fractions for- each risk factor alone, and for the combination of all risk factors, accounting for multicausality and for mediation of the eff ects of BMI by the other three risks. We calculated attributable deaths by multiplying the cause-specifi c population attributable fractions by the number of disease-specifi c deaths. We obtained cause-specifi c mortality from the Global Burden of Diseases, Injuries, and Risk Factors 2010 Study. We propagated the uncertainties of all the inputs to the fi nal estimates. Findings In 2010, high blood pressure was the leading risk factor for deaths due to cardiovascular diseases, chronic kidney disease, and diabetes in every region, causing more than 40% of worldwide deaths from these diseases; high BMI and glucose were each responsible for about 15% of deaths, and high cholesterol for more than 10%. After accounting for multicausality, 63% (10\ub78 million deaths, 95% CI 10\ub71\u201311\ub75) of deaths from these diseases in 2010 were attributable to the combined eff ect of these four metabolic risk factors, compared with 67% (7\ub71 million deaths, 6\ub76\u20137\ub76) in 1980. The mortality burden of high BMI and glucose nearly doubled from 1980 to 2010. At the country level, age-standardised death rates from these diseases attributable to the combined eff ects of these four risk factors surpassed 925 deaths per 100 000 for men in Belarus, Kazakhstan, and Mongolia, but were less than 130 deaths per 100 000 for women and less than 200 for men in some high-income countries including Australia, Canada, France, Japan, the Netherlands, Singapore, South Korea, and Spain. Interpretation The salient features of the cardiometabolic disease and risk factor epidemic at the beginning of the 21st century are high blood pressure and an increasing eff ect of obesity and diabetes. The mortality burden of cardiometabolic risk factors has shifted from high-income to low-income and middle-income countries. Lowering cardiometabolic risks through dietary, behavioural, and pharmacological interventions should be a part of the globalresponse to non-communicable diseases

Genome-wide association study of the modified Stumvoll Insulin Sensitivity Index identifies BCL2 and FAM19A2 as novel insulin sensitivity loci

Genome-wide association studies (GWAS) have found few common variants that influence fasting measures of insulin sensitivity. We hypothesized that a GWAS of an integrated assessment of fasting and dynamic measures of insulin sensitivity would detect novel common variants. We performed GWAS of the modified Stumvoll Insulin Sensitivity Index (ISI) within the Meta-Analyses of Glucose and Insulin-related traits Consortium. Discovery was performed in 16,753 individuals, and replication was attempted for the 23 most significant novel loci in 13,354 independent individuals. Association with ISI was tested in models adjusted for age, sex, body mass index (BMI) and in a model ("Model 3") analyzing the combined influence of the genotype effect adjusted for BMI and the interaction effect between the genotype and BMI on ISI. In Model 3, three variants reached genome-wide significance: rs13422522 (NYAP2, P=8.87 ×10(-11)), rs12454712 (BCL2, P=2.7×10(-8)) and rs10506418 (FAM19A2, P=1.9×10(-8)). The association at NYAP2 was eliminated by conditioning on the known IRS1 insulin sensitivity locus; the BCL2 and FAM19A2 associations were independent of known cardio-metabolic loci. In conclusion, we identified two novel loci and replicated known variants associated with insulin sensitivity. Further studies are needed to clarify the causal variant and function at the BCL2 and FAM19A2 loci