A dysregulation in CES1, APOE and other lipid metabolism-related genes is associated to cardiovascular risk factors linked to obesity

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

Cerium oxide nanoparticles regulate insulin sensitivity and oxidative markers in 3T3-L1 adipocytes and C2C12 myotubes

Insulin resistance is associated with oxidative stress, mitochondrial dysfunction, and a chronic low-grade inflammatory status. In this sense, cerium oxide nanoparticles (CeO2 NPs) are promising nanomaterials with antioxidant and anti-inflammatory properties. Thus, we aimed to evaluate the effect of CeO2 NPs in mouse 3T3-L1 adipocytes, RAW 264.7 macrophages, and C2C12 myotubes under control or proinflammatory conditions. Macrophages were treated with LPS, and both adipocytes and myotubes with conditioned medium (25% LPS-activated macrophages medium) to promote inflammation. CeO2 NPs showed a mean size of ≤25.3 nm (96.7%) and a zeta potential of mV, suitable for cell internalization. CeO2 NPs reduced extracellular reactive oxygen species (ROS) in adipocytes with inflammation while increased in myotubes with control medium. The CeO2 NPs increased mitochondrial content was observed in adipocytes under proinflammatory conditions. Furthermore, the expression of Adipoq and Il10 increased in adipocytes treated with CeO2 NPs. In myotubes, both Il1b and Adipoq were downregulated while Irs1 was upregulated. Overall, our results suggest that CeO2 NPs could potentially have an insulin-sensitizing effect specifically on adipose tissue and skeletal muscle. However, further research is needed to confirm these findings

Intervención dietético-nutricional en la prevención de la deficiencia de hierro

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

The association of parental genetic, lifestyle, and social determinants of health with offspring overweight

In the UK, the number of comorbidities seen in children has increased along with the worsening obesity rate. These comorbidities worsen into adulthood. Genomewide association studies have highlighted single nucleotide polymorphisms associated with the weight status of adults and offspring individually. To date, in the UK, parental genetic, lifestyle, and social determinants of health have not been investigated alongside one another as influencers of offspring weight status. A comprehensive obesity prevention scheme would commence prior to conception and involve parental intervention including all known risk factors. This current study aims to identify the proportion of overweight that can be explained by known parental risk factors, including genetic, lifestyle, and social determinants of health with offspring weight status in the UK. Methods: A crosssectional study was carried out on 123 parents. Parental and offspring anthropometric data and parental lifestyle and social determinants of health data were self-reported. Parental genetic data were collected by use of GeneFiX saliva collection vials and genotype were assessed for brain-derived neurotrophic factor (BDNF) gene rs6265, melanocortin 4 receptor (MC4R) gene rs17782313, transmembrane protein 18 (TMEM18) gene rs2867125, and serine/threonine-protein kinase (TNN13K) gene rs1514175. Associations were assessed between parental data and the weight status of offspring. Results: Maternal body mass index modestly predicted child weight status (p < 0.015; R2 = 0.15). More mothers of overweight children carried the MC4R rs17782313 risk allele (77.8%; p = 0.007) compared to mothers of normal-weight children. Additionally, fathers who were not Caucasian and parents who slept for < 7 h/night had a larger percentage of overweight children when compared to their counterparts (p = 0.039; p = 0.014, respectively). Conclusion: Associations exist between the weight status of offspring based solely on parental genetic, lifestyle, and social determinants of health data. Further research is required to appropriately address future interventions based on genetic and lifestyle risk groups on a pre-parent cohort

Impact of sarcopenia and frailty in a multicenter cohort of polypathological patients

The prevalence, relationships and outcomes of sarcopenia and frailty in polypathological patients remain unknown. We performed a multicenter prospective observational study in six hospitals in order to assess prevalence, clinical features, outcome and associated risk factors of sarcopenia and frailty in a hospital-based population of polypathological patients. The cohort was recruited by performing prevalence surveys every 14 days during the inclusion period (March 2012-June 2016). Sarcopenia was assessed by means of EWGSOP criteria and frailty by means of Fried''s criteria. Skeletal muscle mass was measured by tetrapolar bioimpedanciometry. All patients were followed for 12 months. Factors associated with sarcopenia, frailty and mortality were analyzed by multivariate logistic regression, and Kaplan-Meier curves. A total of 444 patients (77.3 +/- 8.4 years, 55% males) were included. Sarcopenia was present in 97 patients (21.8%), this being moderate in 54 (12.2%), and severe in 43 (9.6%); frailty was present in 278 patients (62.6%), and 140 (31.6%) were pre-frail; combined sarcopenia and frailty were present in the same patient in 80 (18%) patients. Factors independently associated to the presence of both, sarcopenia and frailty were female gender, older age, different chronic conditions, poor functional status, low body mass index, asthenia and depressive disorders, and low leucocytes and lymphocytes count. Mortality in the 12-months follow-up period was 40%. Patients with sarcopenia, frailty or both survived significantly less than those without these conditions. Sarcopenia and frailty are frequent and interrelated conditions in polypathological patients, shadowing their survival. Their early recognition and management could improve health-related outcomes in this population

Effects of hyperoxia exposure on metabolic markers and gene expression in 3T3- L1 adipocytes

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

Differential proinflammatory and oxidative stress response and vulnerability to metabolic syndrome in habitual high-fat young male consumers putatively predisposed by their genetic background

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

Impact of hypoxia exposure, combined with induced maternal obesity, on gestating sprague dawley dams

Abstract 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

Extensive antimicrobial resistance mobilization via Multicopy Plasmid Encapsidation mediated by temperate phages

Objectives: To investigate the relevance of multicopy plasmids in antimicrobial resistance and assess their mobilization mediated by phage particles Methods: Several databases with complete sequences of plasmids and annotated genes were analysed. The 16S methyltransferase gene armA conferring high-level aminoglycoside resistance was used as a marker in eight different plasmids, from different incompatibility groups, and with differing sizes and plasmid copy numbers. All plasmids were transformed into Escherichia coli bearing one of four different lysogenic phages. Upon induction, encapsidation of armA in phage particles was evaluated using qRT-PCR and Southern blotting. Results: Multicopy plasmids carry a vast set of emerging clinically important antimicrobial resistance genes. However, 60% of these plasmids do not bear mobility (MOB) genes. When carried on these multicopy plasmids, mobilization of a marker gene armA into phage capsids was up to 10000 times more frequent than when it was encoded by a large plasmid with a low copy number. Conclusions: Multicopy plasmids and phages, two major mobile genetic elements (MGE) in bacteria, represent a novel high-efficiency transmission route of antimicrobial resistance genes that deserves further investigation