Assessment of the risk of Hepatitis E virus occurrence in pork carcasses at slaughter in the UK

Hepatitis E virus (HEV) is a RNA virus of the genus Hepevirus. HEV genotype 3 is zoonotic and pigs are the main reservoir. This genotype has been identified in the United Kingdom, in sporadic locally-acquired cases without recent history of foreign travel to endemic countries. The number of HEV-confirmed human cases in the UK has increased significantly, from 124 cases in 2003 to 661 in 2013. Non-travel cases now account for the majority (69%) of cases observed annually in the UK. Our aim was to assess the risk of HEV occurrence in pork carcases at slaughter in the UK. We performed a quantitative exposure assessment using Monte Carlo simulation to estimate the number of carcasses contaminated with HEV produced in a high throughput porcine abattoir during one year. The input data used were: a) true prevalence in British pigs, b) probability of viral shedding in bile and faeces c) number of pig carcases with bile and/or faecal contamination detected during post-mortem inspection. The following assumptions were made when data were unavailable: a) sensitivity and specificity of the RP-PCR diagnostic test; b) meat from viraemic pigs was considered HEV-positive; c) visual faecal and bile contamination only considered since microscopic contamination would not be detected through visual inspection. We estimated through our model that 175,152 (2.4%) of carcases produced in high throughput abattoirs would be infected with HEV in one year period. The number of viraemic pigs slaughtered at the abattoir was the largest driver of the uncertainty in carcass contamination. Variations in this parameter would change the output from 62,982 carcasses up to 306,320. Mitigation strategies at farm level should be explored, as it appears that control at this level would likely result in a higher reduction in HEV contamination in pork meat

Molecular Mechanisms Underlying the Effects of Olive Oil Triterpenic Acids in Obesity and Related Diseases

Dietary components exert protective effects against obesity and related metabolic and cardiovascular disturbances by interfering with the molecular pathways leading to these pathologies. Dietary biomolecules are currently promising strategies to help in the management of obesity and metabolic syndrome, which are still unmet medical issues. Olive oil, a key component of the Mediterranean diet, provides an exceptional lipid matrix highly rich in bioactive molecules. Among them, the pentacyclic triterpenic acids (i.e., oleanolic acid) have gained clinical relevance in the last decade due to their wide range of biological actions, particularly in terms of vascular function, obesity and insulin resistance. Considering the promising effects of these triterpenic compounds as nutraceuticals and components of functional foods against obesity and associated complications, the aim of our review is to decipher and discuss the main molecular mechanisms underlying these effects driven by olive oil triterpenes, in particular by oleanolic acid. Special attention is paid to their signaling and targets related to glucose and insulin homeostasis, lipid metabolism, adiposity and cardiovascular dysfunction in obesity. Our study is aimed at providing a better understanding of the impact of dietary components of olive oil in the long-term management of obesity and metabolic syndrome in humans

Targeting AgRP neurons to maintain energy balance: lessons from animal models

The current obesity epidemic is a major worldwide health and economic burden. In the modern environment, an increase in the intake of high-fat and high-sugar foods plays a crucial role in the development of obesity by disrupting the mechanisms governing food intake and energy balance. Food intake and whole-body energy balance are regulated by the central nervous system through a sophisticated neuronal network located mostly in the hypothalamus. In particular, the hypothalamic arcuate nucleus (ARC) is a fundamental center that senses hormonal and nutrient-related signals informing about the energy state of the organism. The ARC contains two small, defined populations of neurons with opposite functions: anorexigenic proopiomelanocortin (POMC)-expressing neurons and orexigenic Agouti-related protein (AgRP)-expressing neurons. AgRP neurons, which also co-produce neuropeptide Y (NPY) and γ-Aminobutyric acid (GABA), are involved in an increase in hunger and a decrease in energy expenditure. In this review, we summarize the key findings from the most common animal models targeting AgRP neurons and the tools used to discern the role of this specific neuronal population in the control of peripheral metabolism, appetite, feeding-related behavior, and other complex behaviors. We also discuss how knowledge gained from these studies has revealed new pathways and key proteins that could be potential therapeutic targets to reduce appetite and food addictions in obesity and other diseases

Small-scale pig farmers’ behavior, silent release of African swine fever virus and consequences for disease spread

The expanding distribution of African swine fever (ASF) is threatening the pig industry worldwide. Most outbreaks occur in backyard and small-scale herds, where poor farmers often attempt to limit the disease’s economic consequences by the emergency sale of their pigs. The risk of African swine fever virus (ASFV) release via this emergency sale was investigated. Simulation modeling was used to study ASFV transmission in backyard and small-scale farms as well as the emergency sale of pigs, and the potential impact of improving farmers and traders’ clinical diagnosis ability–its timeliness and/or accuracy–was assessed. The risk of ASFV release was shown to be high, and improving farmers’ clinical diagnosis ability does not appear sufficient to effectively reduce this risk. Estimates obtained also showed that the distribution of herd size within the backyard and small-scale sectors influences the relative contribution of these farms to the risk of release of infected pigs. These findings can inform surveillance and control programs

New approaches targeting brown adipose tissue transplantation as a therapy in obesity

Brown adipose tissue (BAT) is raising high expectations as a potential target in the fight against metabolic disorders such as obesity and type 2 diabetes. BAT utilizes fuels such as fatty acids to maintain body temperature by uncoupling mitochondrial electron transport to produce heat instead of ATP. This process is called thermogenesis. BAT was considered to be exclusive to rodents and human neonates. However, in the last decade several studies have demonstrated that BAT is not only present but also active in adult humans and that its activity is reduced in several pathological conditions, such as aging, obesity, and diabetes. Thus, tremendous efforts are being made by the scientific community to enhance either BAT mass or activity. Several activators of thermogenesis have been described, such as natriuretic peptides, bone morphogenic proteins, or fibroblast growth factor 21. Furthermore, recent studies have tested a therapeutic approach to directly increase BAT mass by the implantation of either adipocytes or fat tissue. This approach might have an important future in regenerative medicine and in the fight against metabolic disorders. Here, we review the emerging field of BAT transplantation including the various sources of mesenchymal stem cell isolation in rodents and humans and the described metabolic outcomes of adipocyte cell transplantation and BAT transplantation in obesity. KEYWORDS: Brown adipose tissue; Obesity; Transplantatio

High-Intensity Exercise Reduces Cardiac Fibrosis and Hypertrophy but Does Not Restore the Nitroso-Redox Imbalance in Diabetic Cardiomyopathy

Diabetic cardiomyopathy refers to the manifestations in the heart as a result of altered glucose homeostasis, reflected as fibrosis, cellular hypertrophy, increased oxidative stress, and apoptosis, leading to ventricular dysfunction. Since physical exercise has been indicated as cardioprotective, we tested the hypothesis that high-intensity exercise training could reverse the cardiac maladaptations produced by diabetes. For this, diabetes was induced in rats by a single dose of alloxan. Diabetic rats were randomly assigned to a sedentary group or submitted to a program of exercise on a treadmill for 4 weeks at 80% of maximal performance. Another group of normoglycemic rats was used as control. Diabetic rat hearts presented cardiomyocyte hypertrophy and interstitial fibrosis. Chronic exercise reduced both parameters but increased apoptosis. Diabetes increased the myocardial levels of the mRNA and proteins of NADPH oxidases NOX2 and NOX4. These altered levels were not reduced by exercise. Diabetes also increased the level of uncoupled endothelial nitric oxide synthase (eNOS) that was not reversed by exercise. Finally, diabetic rats showed a lower degree of phosphorylated phospholamban and reduced levels of SERCA2 that were not restored by high-intensity exercise. These results suggest that high-intensity chronic exercise was able to reverse remodeling in the diabetic heart but was unable to restore the nitroso-redox imbalance imposed by diabetes

High-Intensity Exercise Reduces Cardiac Fibrosis and Hypertrophy but Does Not Restore the Nitroso-Redox Imbalance in Diabetic Cardiomyopathy

Diabetic cardiomyopathy refers to the manifestations in the heart as a result of altered glucose homeostasis, reflected as fibrosis, cellular hypertrophy, increased oxidative stress, and apoptosis, leading to ventricular dysfunction. Since physical exercise has been indicated as cardioprotective, we tested the hypothesis that high-intensity exercise training could reverse the cardiac maladaptations produced by diabetes. For this, diabetes was induced in rats by a single dose of alloxan. Diabetic rats were randomly assigned to a sedentary group or submitted to a program of exercise on a treadmill for 4 weeks at 80% of maximal performance. Another group of normoglycemic rats was used as control. Diabetic rat hearts presented cardiomyocyte hypertrophy and interstitial fibrosis. Chronic exercise reduced both parameters but increased apoptosis. Diabetes increased the myocardial levels of the mRNA and proteins of NADPH oxidases NOX2 and NOX4. These altered levels were not reduced by exercise. Diabetes also increased the level of uncoupled endothelial nitric oxide synthase (eNOS) that was not reversed by exercise. Finally, diabetic rats showed a lower degree of phosphorylated phospholamban and reduced levels of SERCA2 that were not restored by high-intensity exercise. These results suggest that high-intensity chronic exercise was able to reverse remodeling in the diabetic heart but was unable to restore the nitroso-redox imbalance imposed by diabetes

.Efecto protector del extracto de propóleos sobre la célula β pancreática sometida a estrés oxidativo

73 p.Introducción: Se ha reportado que tanto la glucotoxicidad y la lipotoxicidad, tienen una estrecha relación con el estrés oxidativo en la célula β pancreática, que altera su funcionalidad y empeora la progresión de la enfermedad; por lo que sería importante aumentar el potencial antioxidante para prevenir los efectos deletéreos del estrés oxidativo generado durante la progresión de la patología. En el presente estudio se evaluó el efecto del extracto de propóleos sobre el estrés oxidativo inducido en células β pancreáticas. Objetivos: Evaluar el efecto antioxidante de un extracto de propóleos frente al estrés oxidativo inducido por H2O2 y t-BOOH en células β pancreáticas de la línea MIN-6 y β TC-6 de ratón. Métodos: Se realizó un ensayo de MTT para evaluar la viabilidad de las células MIN-6 y β TC-6 cultivada en medio DMEM-H, bajo distintas condiciones. Se midieron las sustancias reactivas del ácido tiobarbiturico (TBARs), glutatión reducido intracelular (GSH) y se midió la apoptosis a través de citometría de flujo utilizando marcación con Anexina-V y Yoduro de Propidio (IP). Resultados: Las células MIN-6 y β TC-6 expuestas a 150 μM de H2O2 y 100 μM de t-BOOH redujeron significativamente la viabilidad celular (p < 0,05) de forma tiempo dependiente. No se observaron efectos citotóxicos in vitro al exponer las células MIN-6 y β TC-6 a concentraciones de 20 y 40 μg/ml de compuestos fenólicos presentes en el extracto de propóleos. Concentraciones superiores reducen significativamente la viabilidad celular. Cuando las células fueron incubadas simultáneamente con extracto de propóleos y oxidantes, mantuvieron la viabilidad celular respecto al control. La exposición de las células en cultivo a los oxidantes, aumentaron los niveles de TBARs y se redujo la concentración de GSH, condición que se revirtió cuando fueron incubados con extracto de propóleos. Se observó un aumento significativo de células β TC-6 anexina-V positivas (apoptóticas) cuando fueron expuestas a los oxidantes, sin embargo la exposición a extracto de propóleos redujo la cantidad de células apoptóticas. Conclusión: El H2O2 y t-BOOH, a una concentración de 150 y 100 μM respectivamente, reducen significativamente la viabilidad celular y la concentración de 10 GSH. Además, aumentan los niveles de TBARs y el número de células β pancreáticas apoptóticas. El extracto de propóleos a una concentración de 20 y 40 μg/ml de compuestos fenólicos, mantiene la viabilidad de las células β pancreáticas y los niveles de GSH, previene el aumento de TBARs y reduce el número de células apoptóticas

Moderate SIRT1 overexpression protects against brown adipose tissue inflammation

Objective: Metainflammation is a chronic low-grade inflammatory state induced by obesity and associated comorbidities, including peripheral insulin resistance. Brown adipose tissue (BAT), a therapeutic target against obesity, is an insulin target tissue sensitive to inflammation. Therefore, it is demanding to find strategies to protect BAT against the effects of inflammation in energy balance. In this study we have explored the impact of moderate Sirtuin 1 (SIRT1) overexpression in insulin sensitivity and β-adrenergic responses in BAT and brown adipocytes (BA) under pro-inflammatory conditions. Methods: The effect of inflammation in BAT functionality was studied in obese db/db mice and lean wild-type (WT) mice or mice with moderate overexpression of SIRT1 (SIRT1Tg+) injected a low dose of bacterial lipopolysaccharide (LPS) to mimic endotoxemia. We also conducted studies in differentiated BA (BA-WT and BA-SIRT1Tg+) exposed to a macrophagederived pro-inflammatory conditioned medium (CM) to evaluate the protection of SIRT1 overexpression in insulin signaling and glucose uptake, mitochondrial respiration, fatty acid oxidation (FAO), as well as norepinephrine (NE)-mediated-modulation of uncoupling protein-1 (UCP-1) expression. Results: BAT from db/db mice was susceptible to metabolic inflammation manifested by activation of pro-inflammatory signaling cascades, increased pro-inflammatory gene expression, tissue-specific insulin resistance and reduced UCP-1 expression. Impairment of insulin and noradrenergic responses were also found in lean WT mice upon LPS injection. By contrast, BAT from mice with moderate overexpression of SIRT1 (SIRT1Tg+) was protected against LPSinduced activation of pro-inflammatory signaling, insulin resistance and defective thermogenicrelated responses upon cold exposure. Importantly, the drop of triiodothyronine (T3) levels both in circulation and intra-BAT after exposure of WT mice to LPS and cold was markedly attenuated in SIRT1Tg+ mice. In vitro experiments in BA from the two genotypes revealed that upon differentiation with a T3-enriched medium and subsequent exposure to a macrophagederived pro-inflammatory CM, only BA-SIRT1Tg+ fully recovered insulin and noradrenergic responses. Conclusion: This study has unraveled the benefit of moderate overexpression of SIRT1 to confer protection against defective insulin and β-adrenergic responses caused by inflammation in BAT. Our results have potential therapeutic value proposing combinatorial therapies of BATspecific thyromimetics and SIRT1 activators to combat metainflammation in this tissue

Ghrelin causes a decline in GABA release by reducing fatty acid oxidation in cortex

Lipid metabolism, specifically fatty acid oxidation (FAO) mediated by carnitine palmitoyltransferase (CPT) 1A, has been described to be an important actor of ghrelin action in hypothalamus. However, it is not known whether CPT1A and FAO mediate the effect of ghrelin on the cortex. Here, we show that ghrelin produces a differential effect on CPT1 activity and γ-aminobutyric acid (GABA) metabolism in the hypothalamus and cortex of mice. In the hypothalamus, ghrelin enhances CPT1A activity while GABA transaminase (GABAT) activity, a key enzyme in GABA shunt metabolism, is unaltered. However, in cortex CPT1A activity and GABAT activity are reduced after ghrelin treatment. Furthermore, in primary cortical neurons, ghrelin reduces GABA release through a CPT1A reduction. By using CPT1A floxed mice, we have observed that genetic ablation of CPT1A recapitulates the effect of ghrelin on GABA release in cortical neurons, inducing reductions in mitochondrial oxygen consumption, cell content of citrate and α-ketoglutarate, and GABA shunt enzyme activity. Taken together, these observations indicate that ghrelin-induced changes in CPT1A activity modulate mitochondrial function, yielding changes in GABA metabolism. This evidence suggests that the action of ghrelin on GABA release is region specific within the brain, providing a basis for differential effects of ghrelin in the central nervous system. Keywords: Ghrelin, GABA, Fatty acid oxidation, CPT1A, Cortical neuron