Search

La cardiopatía isquémica y el accidente cerebrovascular se presentan como las primeras causas de muerte a nivel mundial. El desarrollo de ambas está condicionado por múltiples factores de riesgo, entre los que destaca el estado inflamatorio sistémico propio de pacientes obesos, que lleva a la progresión de la aterosclerosis. Profundizar en los mecanismos de esta relación resulta fundamental para el desarrollo de nuevas herramientas terapéuticas y profilácticas. Distintas investigaciones han demostrado la eficacia de la suplementación con ácidos grasos omega 3 en la disminución del estado inflamatorio, así como su acción sobre el metabolismo de los lípidos. Uno de los mecanismos que se han sugerido es que pueda actuar sobre la respuesta celular a la hipoxia que, en el tejido adiposo, podría ser la principal desencadenante de la inflamación y que determinará la evolución de los pacientes con cardiopatía isquémica o accidente cerebrovascular, que no suponen otra cosa que la interrupción del flujo sanguíneo a nivel coronario o cerebral. En este contexto, la presente revisión pretende determinar el estado de la investigación sobre el empleo de ácidos grasos omega 3 en el tratamiento y prevención de las principales enfermedades cardiovasculares por sus acciones frente a la hipoxia. A pesar de la heterogeneidad de los artículos revisados parece claro el efecto beneficioso de los ácidos grasos omega 3, aunque pocos parecen relacionarlo con su acción frente a la hipoxia. En estos últimos parece que el efecto estaría mediado por la angiogénesis y la actividad de VEGF y quizá podría estar implicada la regulación de HIF-1α. Si bien, parece clara la necesidad de una mayor investigación en este campo para detallar los mecanismos por los que actúan los omega 3 y la relación que podrían tener con la hipoxia. Ischemic heart disease and stroke are the leading causes of death worldwide. The development of both is conditioned by multiple risk factors, among which, the systemic inflammatory state characteristic of obese patients stands out, which leads to the progression of atherosclerosis. Studying the mechanisms of this relationship in depth is essential for the development of new therapeutic and prophylactic tools. Various investigations have shown the efficacy of omega 3 fatty acid supplementation in reducing the inflammatory state, as well as its action on lipid metabolism. One of the mechanisms that have been suggested is that it can act on the cellular response to hypoxia that, in adipose tissue, could be the main trigger for inflammation and that will determine the evolution of patients with ischemic heart disease or stroke, which only consist on the interruption of blood flow at coronary or cerebral level. In this context, this review aims to determine the state of the research on the use of omega 3 fatty acids in the treatment and prevention of the main cardiovascular diseases due to their actions against hypoxia. Despite the heterogeneity of the articles reviewed, the beneficial effect of omega 3 fatty acids seems clear, although few seem to relate these to their action against hypoxia. In the latter, it appears that the effect would be mediated by angiogenesis and VEGF activity, and perhaps, HIF-1α regulation might be involved. In any case, it seems clear the need for further research in this field to detail the mechanisms by which omega 3 act, and the relationship that they could have with hypoxia.

Fundamento: El Ramadán, es un tipo de ayuno religioso muy extendido entre la población deportista tanto a nivel popular como a nivel profesional. Esta práctica puede suponer un “hándicap” para los deportistas, especialmente los de más alto nivel, ya que hay estudios que afirman que podría tratarse de una práctica perjudicial para su rendimiento deportivo. Por esta razón, es pertinente analizar los posibles efectos que puede tener esta práctica sobre las capacidades aeróbicas y anaeróbicas y las posibles modificaciones que podrían dar pie a minimizar este posible efecto deletéreo. En base a esto, el objetivo de esta revisión sistemática es analizar la evidencia existente sobre los posibles efectos del Ramadán sobre el rendimiento deportivo. Metodología: Se realizó una revisión sistemática utilizando la base de datos PubMed como principal buscador. La revisión siguió la metodología Prisma, y los términos utilizados para dicha revisión fueron: Effects of Ramadán AND performance. Resultados: Se obtuvieron un total de 18 artículos que analizaban los efectos del Ramadán sobre distintas variables del rendimiento deportivo en atletas aficionados y profesionales. El resultado obtenido en general es controvertido. A día de hoy no está claro si los efectos del Ramadán sobre los deportistas son significativos como para traducirse en un menor rendimiento físico. Conclusión: Por un lado, podría existir cierto efecto del Ramadán sobre el rendimiento deportivo, especialmente sobre el aeróbico. No obstante, esto aún no está claro. Por esta razón son necesarios más estudios que decanten la balanza hacia uno u otro lado. No obstante, es conveniente optimizar el entorno que rodea a este tipo de ayuno, para que, en el caso de tener algún efecto perjudicial, este sea mínimo. Especialmente cuando se trata de deportistas de alto nivel en los que un pequeño efecto puede resultar decisivo. Background: Ramadan fasting is very widespread between professional and amateur athletes. This kind of fasting could have a detrimental effect over sport performance. This is the reason why it could be very interesting to analyze the potential negative effects that this could have over the sport performance. Even more if we take into account the impact that could have even a very small effect among professional or high-level athletes. For this reason, it is relevant to review the present knowledge available in terms of the effect of the Ramadan fasting over the aerobic and the anaerobic capacities and the possible strategies to minimize the yet controversial negative effect. For this reason, the aim of this systematic review is to analyze the available evidence about the potential detrimental effects of the Ramadan fasting over the sports performance. Methodology: A systematic review was performed using the PubMed database as the main searching tool. The review used the Prisma methodology, and the key word used for the research were: Effects of Ramadan AND performance. Results: A total of 18 articles were included in the systematic review. They analyzed the effect of Ramadan fasting on different variables of sport performance in amateur and professional athletes. The overall results are controversial. It is not clear that the effects of the Ramadan fasting are enough to translate into a lower physical performance. Conclusion: On the one hand, there could be some negative effect of Ramadan on sport performance, especially aerobic performance. However, this is unclear and more studies are needed to explain the role Ramadan could have over athlete’s performance. However, it is convenient to optimize the environment that surrounds this practice in case there is little effect. Even more if we are dealing with professional athletes.

The journal NUTRIENTS published some time ago a special issue about “Precision Nutrition and Metabolic Syndrome Management”, which included a series of articles about the role of bioactive compounds, amino acids/proteins and fatty acids for personalized nutritional applications [1]. In such volume, the emerging concept of precision nutrition was developed in two specific reviews. These articles explain global personalized nutrition in the management of metabolic syndrome features such as obesity, diabetes, dyslipemia, hypertension and other cardiovascular complications [2], and individualized lipid metabolism targeting in cancer [3]. In particular, they describe the role of nutrigenetics, deep phenotyping, family and personal clinical cues, perinatal nutrition and a wide spectrum of data concerning metabolic personalization through omics technologies (metabolomics, epigenomics, metagenomics, and others), whose possibilities were appraised. Indeed, the conceptual framework understanding precision nutrition is based on assessing the interindividual heterogeneity caused by genetic/epigenetic dissimilarities, the lifestyle and environmental exposome diversity, microbiome variations, and singular behavioral/psychological features [4] with clear implications for public health to harmonize personal and population challenges and applications [5].

The presence of oxygen in our atmosphere is and has been vital for evolution and survival, not only for humans, but for the majority of living beings on Earth. In this sense, world renowned scientists have revealed that several metabolic disorders present altered oxygen partial pressure at a tissue level, while some researchers have re-considered oxygen as a nutrient. Oxygen availability could be compromised in obesity and several other metabolically related pathological manifestations such as: sleep apnea-hypopnea syndrome (SAHS), metabolic syndrome (Mets, which is a set of conditions, including: hyperglycemia, hypertension, hyperlipemia, and central adiposity), diabetes type 2 and cardiovascular disease. Strategies designed to reduce adiposity and accompanying manifestations have been mainly based on nutritional interventions and physical activity programs. However, novel therapies are needed since these approaches have not been sufficient to counteract the increasing rates of metabolic disorders. In this regard, a potential treatment is intermittent hypoxia training, which could induce several benefits from oxygen-related adaptations. Concerning prevention, other authors have reported that living at high altitude could have a protective effect against the development of abnormal metabolic conditions. On the other hand, there is a growing need for novel in vitro models to study the potential pathways involved in metabolic dysfunction in order to find appropriate therapeutic targets. Based on the existing evidence, it was theorized that the oxygen availability has a key role in obesity and related comorbidities. Thus, the general objective of the present dissertation was to investigate the implication of oxygen on metabolic disorders in vivo and in vitro. Overall, the results reported in the present dissertation evidenced the involvement of oxygen in obesity and associated metabolic disorders. Notably, individuals with obesity coupled to SAHS, showed specific cardiometabolic benefits from the treatment with intermittent hypoxia training. Moreover, our research adds novel data to the existing literature concerning the epigenetic markers and metabolic disease, as participants with lower resting oxygen consumption showed lower IL6 methylation and higher IL-6 serum levels, normally related with a pro-inflammatory status. Furthermore, the incidence and prevalence of MetS was inversely associated to altitude both in Spain and Ecuador, suggesting a physiological protective role of geographical elevation on metabolic disorders. These results confirm that oxygen availability could be one of the main features to understand, prevent and treat metabolic disorders. Furthermore, our research contributed to better comprehend not only the participation of oxygen levels in the air breathed, but also the cellular and molecular involvement of oxygen in inflammation through HIF-1α transcriptional activation, the master regulator of oxygen homeostasis. The CM in vitro model showed great similarities to the HFD mice models, commonly used in the study of obesity and related pathologies. Finally, the treatment with cerium oxide nanoparticles in metabolic syndrome-related cell lines under pro-inflammatory conditions suggested a potential insulin sensitizing effect specifically on adipose tissue and skeletal muscle as related to mitochondrial content and adiponectin expression. In conclusion, oxygen arises as a good option to further investigate not only the potential therapeutic strategies, but also new targets in the treatment and prevention of metabolic disorders.

BACKGROUND: Residence at high altitude has been associated with lower obesity rates probably due to hypoxia conditions. However, there is no evidence of this association in a free-living population. OBJECTIVES: We assessed the association between the altitude where each participant of a Spanish cohort (the SUN Project) was living and the incidence of overweight/obesity. METHODS: The SUN Project is a dynamic, prospective, multipurpose cohort of Spanish university graduates with a retention rate of 89%. We included in the analysis 9 365 participants free of overweight/obesity at baseline. At the baseline questionnaire, participants reported their postal code and the time they had been living in their city/village. We imputed the altitude of each postal code according to the data of the Spanish National Cartographic Institute and categorized participants in tertiles. We used Cox regression models to adjust for potential confounding variables. RESULTS: During a median follow-up of 10 years, we identified 2 156 incident cases of overweight/obesity. After adjusting for sex, age, time of residence at current city, baseline body mass index, physical activity, sedentarism and years of education (≤ 3 years, ≥ 4 years, Master/PhD), those participants in the third tertile (>456 m) exhibited a statistically significant 14% reduction in the risk of developing overweight/obesity in comparison to those in the first tertile (

Obesity is now considered to be a global epidemic, impacting a great number of women and leading to a higher risk of obstetrical and gestational complications. One of such possible adverse outcomes in gestating female is placental hypoxia, which has been related to vascular remodeling and hypertension, as well as adaptive phenomena to reduce levels of oxidative stress and damage. A pool of female Sprague Dawley rats (n=63) was first assigned into two dietary groups (Control and High Sugar). Following mating, the pregnant rats (n=39) were again distributed into two oxygen treatment groups (Normoxia and Hypoxia) for 3 weeks, and tissue sampling and biochemical analyses were carried out. The main results of this study are the following: 1) Hypoxia during gestation may lead to a reduction in the average number of pups per mother, 2) Hypoxia during gestation treatment may lead to a decrease in maternal serum TG levels, and consequentially 3) Hypoxia during gestation may lead to a reduction in TyG Index levels. These results suggest that hypoxia could generate a beneficial response in pregnant Sprague Dawley rats to salvage both maternal and fetal viability. Thus, reproducing mild hypoxic conditions could result being a viable therapeutic option in preventing gestational adversities. In conclusion, progress was made in recognizing the possible role of a mild hypoxic environment in stimulating a maternal protective response.

Obesity is a major public health problem that commonly leads to the initiation and development of a number of chronic diseases such as type 2 diabetes, cardiovascular diseases and different metabolic syndrome manifestations. Adipose tissue often becomes poorly oxygenated in obese subjects, and this feature may provide cellular mechanisms involving chronic inflammation processes such as the release of pro-inflammatory cytokines and macrophage infiltration. Hypoxia has been shown to reduce appetite and adipose tissue mass in humans at certain circumstances, while hyperoxia can ameliorate the hypoxic state and reduce local inflammation in some cell lines and organs. Thus, the purpose of the present study was to determine whether hypoxia and hyperoxia exposures could induce favorable changes in specific metabolic variables and gene expression pathways in both rats and 3T3-L1 adipocyte models. A cyclic hypoxia (8% O2) produced appetite suppression in rats, leading to a significant decrease in weight gain compared to control group. However, this weight reduction was accompanied by a loss of muscle mass. On the other hand, exposing rats to hyperoxia (40% O2) produced no relevant differences between groups concerning body weight and biochemical values measured after the treatment. In adipocytes exposed to 95% O2 a decrease of lactate production and an increase of glycerol release was found, along with a decrease in the expression of GLUT-1 and ANGPTL4 and an increase in PPAR-γ mRNA levels, suggesting that hyperoxia could exert a beneficial effect on the modulation of the metabolism of glucose and lipids, and may play an indirect role in improving insulin sensitivity.

Human GLUT12 was isolated from the breast cancer cell line MCF-7 by its homology with GLUT4. Glucose has been described as its main substrate, but it also can transport other sugars. In humans, GLUT12 protein is expressed mainly in insulin sensitive tissues. Functional analysis has showed that GLUT12 transports sugars down its concentration gradient, but it can also work as a proton-coupled symporter. Studies from our laboratory, performed in Xenopus laevis oocytes expressing GLUT12, show that glucose uptake increases in the presence of Na+ and induces inward current. These findings suggest a transport mechanism never described for other GLUTs, which would indicate a distinct functional role for GLUT12. In relation with its physiological and pathophysiological function, GLUT12 has been mainly studied due to its role as a secondary insulin-sensitive glucose transporter and its possible implication in impaired insulin signalling pathologies. Its expression in some tumour tissues has been described and recently, it has been proposed as one of the key proteins in the glucose supply to malignant cells. Overall, even though a lot of information about GLUT12 has been released during the last years, its functional characteristics, physiological role or implication in the development of some diseases is still unclear. Therefore, this review of the literature can help to address further investigations needed to elucidate these issues that, in our view, are of great interest mainly due to the direct GLUT12 relation with cancer and probably with diabetes development.

The current nutritional habits and lifestyles of modern societies favor energy overloads and a diminished physical activity, which may produce serious clinical disturbances and excessive weight gain. In order to investigate the mechanisms by which the environmental factors interact with molecular mechanisms in obesity, a pathway analysis was performed to identify genes differentially expressed in subcutaneous abdominal adipose tissue (SCAAT) from obese compared to lean male (21-35 year-old) subjects living in similar obesogenic conditions: habitual high fat dietary intake and moderate physical activity. Genes involved in inflammation (ALCAM, CTSB, C1S, YKL-40, MIF, SAA2), extracellular matrix remodeling (MMP9, PALLD), angiogenesis (EGFL6, leptin) and oxidative stress (AKR1C3, UCHL1, HSPB7 and NQO1) were upregulated; whereas apoptosis, signal transcription (CITED 2 and NR3C1), cell control and cell cycle-related genes were downregulated. Interestingly, the expression of some of these genes (C1S, SAA2, ALCAM, CTSB, YKL-40 and tenomodulin) was found to be associated with some relevant metabolic syndrome features. The obese group showed a general upregulation in the expression of inflammatory, oxidative stress, extracellular remodeling and angiogenic genes compared to lean subjects, suggesting that a given genetic background in an obesogenic environment could underlie the resistance to gaining weight and obesity-associated manifestations.

Obesity is an important public health problem worldwide and is a major risk factor for a number of chronic diseases such as type 2 diabetes, adverse cardiovascular events and metabolic syndrome related features. Different treatments have been applied to tackle body fat accumulation and its associated clinical manifestations. Often, relevant weight loss is achieved during the first six months under different dietary treatments. From this point, a plateau is reached, and a gradual recovery of the lost weight may occur. Therefore, new research approaches are being investigated to assure weight maintenance. Pioneering investigations have reported that oxygen variations in organic systems may produce changes in body composition. Possible applications of intermittent hypoxia to promote health and in various pathophysiological states have been reported. The hypoxic stimulus in addition to diet and exercise can be an interesting approach to lose weight, by inducing higher basal noradrenalin levels and other metabolic changes whose mechanisms are still unclear. Indeed, hypoxic situations increase the diameter of arterioles, produce peripheral vasodilatation and decrease arterial blood pressure. Furthermore, hypoxic training increases the activity of glycolytic enzymes, enhancing the number of mitochondria and glucose transporter GLUT-4 levels as well as improving insulin sensitivity. Moreover, hypoxia increases blood serotonin, decreases leptin levels while appetite is suppressed. These observations allow considering the hypothesis that intermittent hypoxia induces fat loss and may ameliorate cardiovascular health, which might be of interest for the treatment of obesity. This new strategy may be useful and practical for clinical applications in obese patients.

Adipose tissue often becomes poorly oxygenated in obese subjects. This feature may provide cellular mechanisms involving chronic inflammation processes such as the release of proinflammatory cytokines and macrophage infiltration. In this context, the purpose of the present study was to determine whether a hyperoxia exposure on mature adipocytes may influence the expression of some adipokines and involve favorable changes in specific metabolic variables. 3T3-L1 adipocytes (14 days differentiated) were treated with 95% oxygen for 24 h. Cell viability, intra and extracellular reactive oxygen especies (ROS) content, glucose uptake and lactate and glycerol concentrations were measured in the culture media. Also, mRNA levels of HIF-1[alfa], leptin, IL-6, MCP-1, PPAR-[gamma], adiponectin, and ANGPTL-4 were analyzed. Hyperoxia treatment increased intra and extracellular ROS content, reduced glucose uptake and lactate release and increased glucose release. It also led to an upregulation of the expression of IL-6, MCP-1 and PPAR-[gamma], while ANGPTL4 was downregulated in the hyperoxia group with respect to control. The present data shows that hyperoxia treatment seems to provoke an inflammatory response due to the release of ROS and the upregulation of pro-inflammatory adipokines, such as IL-6 and MCP-1. On the other hand, hyperoxia may have an indirect effect on the improvement of insulin sensitivity, due to the upregulation of PPAR-[gamma] gene expression as well as a possible modulation of both glucose and lipid metabolic markers. To our knownledge, this is the first study analyzing the effect of hyperoxia in 3T3-L1 adipocytes.

There are major variations in the susceptibility to weight gain among individuals under similar external influences (decreased physical activity and excessive calorie intake), depending on the genetic background. In the present study, we performed a microarray analysis and RT-PCR validations in order to find out differential gene expression in subcutaneous abdominal adipose tissue from two groups of subjects that despite living in similar environmental conditions such as a habitual high fat dietary intake (energy as fat >40%) and similar moderate physical activity, some of them were successfully “resistant” (lean) to weight gain, while others were “susceptible” to fat deposition (obese). The classification of up- and down- regulated genes into different categories together with the analysis of the altered biochemical pathways, revealed a coordinated downregulation of catabolic pathways operating in the mitochondria: fatty acid oxidation (P=0.008), TCA cycle (P=0.001) and electron transport chain (P=0.012). At the same time, glucose metabolism (P=0.010) and fatty acid biosynthesis (P=0.011) pathways were also downregulated in obese compared to lean subjects. In conclusion, our data showed an orchestrated downregulation of nuclear-encoded mitochondrial gene expression. These genes are involved in cellular respiration and oxidative metabolism pathways, and could play a role in the susceptibility to weight gain in some individuals.

En este artículo se expone evidencia científica sobre la anemia ferropénica fundamentalmente desde aspectos dietético-nutricionales que inciden en la biodisponibilidad del hierro de los alimentos. La anemia constituye un problema de salud pública a nivel mundial, padeciéndolo aproximadamente 2000 millones de personas y afectando fundamentalmente a lactantes, ancianos, adolescentes, mujeres en edad fértil y embarazadas. Como consecuencia de esta enfermedad, la capacidad para realizar trabajo físico, la inmunidad celular y la capacidad bactericida de los neutrófilos se ven sensiblemente alteradas. Además, la anemia puede producir: mayor susceptibilidad a infecciones, especialmente, del tracto respiratorio, disminución de la termogénesis en ambientes fríos, alteraciones funcionales del tubo digestivo, fallo en la movilización de la vitamina A hepática, disminución de la velocidad de crecimiento, alteraciones en el desarrollo mental y motor, menor transferencia de hierro al feto, mayor riesgo de parto prematuro o morbilidad perinatal, entre otras. Dentro de los factores que interfieren en la absorción del hierro, los dietéticos son de gran relevancia. Las proteínas cárnicas, ácidos orgánicos, la vitamina C y la A y los fructooligosacáridos (FOS), favorecen su absorción mientras que ciertas proteínas del huevo y de la leche, polifenoles, fitatos, fibra insoluble y minerales como el fósforo, calcio o el zinc, afectan negativamente a la biodisponibilidad del hierro. Las diferentes técnicas culinarias también pueden aumentar o disminuir la biodisponibilidad del hierro. La información recopilada sobre los factores favorecedores e inhibidores de la absorción del hierro, se ha utilizado para, a modo de conclusión, marcar unas pautas dietético-nutricionales para las personas que padecen o tienen predisposición a padecer anemia. This paper outlines the scientific evidence of iron deficiency anemia from dietary and nutritional issues that affect iron-bioavailability from food. Anemia is a worldwide public health problem, with about 2000 million people who suffer from it and mainly affects older infants, adolescents, women of childbearing age and pregnant women. As a consequence of this disease, alterations have been reported: in physical work capacity, cellular immunity and bactericidal capacity of neutrophils. Further more, an increased susceptibility to infections, specially respiratory tract, decreased thermogenesis in cold environments , functional disorders of the gastrointestinal tract, failure in the mobilization of liver vitamin A, decreased growth rate, impaired mental and motor development, less transfer of iron to the fetus, increased risk of preterm delivery, perinatal morbidity, and others. Among the factors that interfere with iron absorption, the diet is one of the most important. Meat proteins, organic acids, vitamin C and A and fructooligosaccharides (FOS), promote the absorption. While egg, milk proteins, polyphenols, phytates, fiber and minerals such as phosphorus, calcium or zinc affect negatively the ironbioavailability. The information collected about the stimulating factors and inhibitors of iron absorption has been used to, as a conclusion, make dietary and nutritional guidelines for those who are predisposed to suffer from anemia.

OBJECTIVE: The aim of the present study was to investigate the relationship between the differential expression of genes related to lipid metabolism in subcutaneous adipose tissue and metabolic syndrome features in lean and obese subjects with habitual high fat intake. METHODS: Microarray and RT-PCR analysis were used to analyze and validate differential gene expression in subcutaneous abdominal adipose tissue samples from lean and obese phenotype subjects. RESULTS: Several genes and transcripts involved in lipolysis were down-regulated, such as AKAP1, PRKAR2B, Gi and CIDEA, whereas NPY1R and CES1 were up-regulated, when comparing obese to lean subjects. Similarly, transcripts associated with cholesterol and lipoprotein metabolism showed a differential expression, with APOE and ABCA being decreased and VLDLR being increased in obese versus lean subjects. In addition, positive correlations were found between different markers of the metabolic syndrome and CES1 and NPY1R mRNA expressions, while APOE showed an inverse association with some of them. CONCLUSION: Different expression patterns in transcripts encoding for proteins involved in lipolysis and lipoprotein metabolism were found between lean and obese subjects. Moreover, the dysregulation of genes such as CES1 and APOE seems to be associated with some physiopathological markers of insulin resistance and cardiovascular risk factors in obesity.

Uncoupling Protein l (UCPl) is an inner mito­ chondrial membrane protein, uniquely expressed in brown adipocytes, which uncouples the mitochondrial respiration impairing ATP production and energy efficiency. The aim of the present study was to express UCPl in liver mitochondria using a non-viral system in order to affect energy utilization. The effect of ectopic protein expression on liver energy metabolism, which was evaluated 42 h after DNA transfer, showed that mitochondria expressing UCPl presented decreased ATP production, lasted more time in membrane potential state 3, and consumed more molecular oxygen to produce the same amount of ATP than the control group. In summary, the successful functionality of the mitochondrial protein, UCPl, after hydrodynamic delivery is a novel and significant finding. This approach could be useful to ectopic­ ally express mitochondrial proteins and, in this particular case, to manage metabolic disorders related to energy efficiency and expenditure, such as obesity.