Mangiferin Decreases Plasma Free Fatty Acids through Promoting Its Catabolism in Liver by Activation of AMPK

Mangiferin has been shown to have the effect of improving dyslipidemia. Plasma free fatty acids (FFA) are closely associated with blood lipid metabolism as well as many diseases including metabolic syndrome. This study is to investigate whether mangiferin has effects on FFA metabolism in hyperlipidemic rats. Wistar rats were fed a high-fat diet and administered mangiferin simultaneously for 6 weeks. Mangiferin (50, 100, 150 mg/kg BW) decreased dose-dependently FFA and triglycerides (TG) levels in plasma, and their accumulations in liver, but increased the β-hydroxybutyrate levels in both plasma and liver of hyperlipidemic rats. HepG2 cells were treated with oleic acid (OA, 0.2 mmol/L) to simulate the condition of high level of plasma FFA in vitro, and were treated with different concentrations of mangiferin simultaneously for 24 h. We found that mangiferin significantly increased FFA uptake, significantly decreased intracellular FFA and TG accumulations in HepG2 cells. Mangiferin significantly increased AMP-activated protein kinase (AMPK) phosphorylation and its downstream proteins involved in fatty acid translocase (CD36) and carnitine palmitoyltransferase 1 (CPT1), but significantly decreased acyl-CoA: diacylgycerol acyltransferase 2 (DGAT2) expression and acetyl-CoA carboxylase (ACC) activity by increasing its phosphorylation level in both in vivo and in vitro studies. Furthermore, these effects were reversed by Compound C, an AMPK inhibitor in HepG2 cells. For upstream of AMPK, mangiferin increased AMP/ATP ratio, but had no effect on LKB1 phosphorylation. In conclusion, mangiferin decreased plasma FFA levels through promoting FFA uptake and oxidation, inhibiting FFA and TG accumulations by regulating the key enzymes expression in liver through AMPK pathway. Therefore, mangiferin is a possible beneficial natural compound for metabolic syndrome by improving FFA metabolism

EPIdemiology of Surgery-Associated Acute Kidney Injury (EPIS-AKI) : Study protocol for a multicentre, observational trial

More than 300 million surgical procedures are performed each year. Acute kidney injury (AKI) is a common complication after major surgery and is associated with adverse short-term and long-term outcomes. However, there is a large variation in the incidence of reported AKI rates. The establishment of an accurate epidemiology of surgery-associated AKI is important for healthcare policy, quality initiatives, clinical trials, as well as for improving guidelines. The objective of the Epidemiology of Surgery-associated Acute Kidney Injury (EPIS-AKI) trial is to prospectively evaluate the epidemiology of AKI after major surgery using the latest Kidney Disease: Improving Global Outcomes (KDIGO) consensus definition of AKI. EPIS-AKI is an international prospective, observational, multicentre cohort study including 10 000 patients undergoing major surgery who are subsequently admitted to the ICU or a similar high dependency unit. The primary endpoint is the incidence of AKI within 72 hours after surgery according to the KDIGO criteria. Secondary endpoints include use of renal replacement therapy (RRT), mortality during ICU and hospital stay, length of ICU and hospital stay and major adverse kidney events (combined endpoint consisting of persistent renal dysfunction, RRT and mortality) at day 90. Further, we will evaluate preoperative and intraoperative risk factors affecting the incidence of postoperative AKI. In an add-on analysis, we will assess urinary biomarkers for early detection of AKI. EPIS-AKI has been approved by the leading Ethics Committee of the Medical Council North Rhine-Westphalia, of the Westphalian Wilhelms-University Münster and the corresponding Ethics Committee at each participating site. Results will be disseminated widely and published in peer-reviewed journals, presented at conferences and used to design further AKI-related trials. Trial registration number NCT04165369

Diferencias sociodemográficas en la adhesión al patrón de dieta mediterránea en poblaciones de España Sociodemographic differences in adherence to the Mediterranean dietary pattern in Spanish populations

Objetivos: Los grupos de nivel social más bajo tienen habitualmente una dieta menos saludable. El objetivo de este estudio es comparar la adhesión al patrón de dieta mediterránea entre diferentes grupos demográficos y sociales de la población adulta. Métodos: Se realizó un estudio transversal en regiones del sur y norte de España, en voluntarios sanos (15.634 varones y 25.812 mujeres) de 29 a 69 años de edad, miembros de la cohorte EPIC en España. Se tuvo en cuenta el consumo de nueve grupos de alimentos para definir el patrón de dieta mediterránea: vegetales, frutas, legumbres, cereales, carne roja, pescado, aceite de oliva, leche y productos lácteos y vino. Se aplicaron dos técnicas de análisis: comparación de la media diaria de consumo de cada grupo, y el cálculo de un escore global para todos los alimentos, por nivel educacional y clase social de origen. Resultados: Los grupos de nivel educacional más bajo consumen mas cereales y legumbres, pero menos vegetales, aceite de oliva (las mujeres), leche y productos lácteos (los varones). El consumo de vino está positivamente asociado con la educación en las mujeres y negativamente asociado en los varones. Calculando una puntuación para medir la adhesión global al patrón de dieta mediterránea, las diferencias por cada grupo de alimentos se compensan, y no hay variaciones según el nivel educacional, aunque existen pequeñas diferencias en la clase social de origen (22,52 en la clase más baja y 21,98 en la clase más alta). El índice de adhesión es más bajo en los adultos jóvenes y mujeres, y ligeramente más alto en las poblaciones del sur (23,53 en Murcia) que en las del norte de España (21,64 en Asturias). Conclusiones: Los resultados sugieren que el patrón de dieta mediterránea es bastante uniforme, al menos en las poblaciones adultas de las áreas incluidas en el estudio.Objectives: Lower social classes tend to eat a less healthy diet. The aim of this study was to compare adherence to the Mediterranean dietary pattern among different demographic and social groups in the adult population. Methods: A cross-sectional study was performed in southern and northern regions of Spain in healthy volunteers (15,634 men and 25,812 women), aged 29-69 years, who were members of the European Prospective Investigation on Cancer cohort in Spain. Nine groups of food were included in the definition of the Mediterranean diet: vegetables and garden products, fruits, pulses, cereals, red meat, fish, olive oil, milk and milk products, and wine. Two techniques were used in the analysis: comparison of the mean daily intake of each group and calculation of an overall score for all the foods according to educational level ang original social class. Results: Groups with the lowest educational levels consumed more cereals and pulses and lower quantities of vegetables, olive oil (women), milk and milk products (men). Wine consumption was positively associated with education in women and was negatively associated in men. Calculation of a score to measure overall adherence to the Mediterranean dietary pattern eliminated differences according to each food category. No variations were found according to educational level, but small differences were found in original social class. The adherence score was lowest in young adults and women and was slightly higher in the south than in the north of Spain. Conclusions: The results suggest that the Mediterranean dietary pattern is fairly uniform, at least in the adult population of the regions included in this study

Fatty acid binding protein is a major determinant of hepatic pharmacokinetics of palmitate and its metabolites

Disposition kinetics of [H-3] palmitate and its low-molecular-weight metabolites in perfused rat livers were studied using the multiple-indicator dilution technique, a selective assay for [H-3] palmitate and its low-molecular-weight metabolites, and several physiologically based pharmacokinetic models. The level of liver fatty acid binding protein (L-FABP), other intrahepatic binding proteins (microsomal protein, albumin, and glutathione S-transferase) and the outflow profiles of [H-3] palmitate and metabolites were measured in four experimentalgroups of rats: 1) males; 2) clofibrate-treated males; 3) females; and 4) pregnant females. A slow-diffusion/bound model was found to better describe the hepatic disposition of unchanged [H-3] palmitate than other pharmacokinetic models. The L-FABP levels followed the order: pregnant female > clofibrate-treated male > female > male. Levels of other intrahepatic proteins did not differ significantly. The hepatic extraction ratio and mean transit time for unchanged palmitate, as well as the production of low-molecular-weight metabolites of palmitate and their retention in the liver, increased with increasing L-FABP levels. Palmitate metabolic clearance, permeability-surface area product, retention of palmitate by the liver, and cytoplasmic diffusion constant for unchanged [H-3] palmitate also increased with increasing L-FABP levels. It is concluded that the variability in hepatic pharmacokinetics of unchanged [H-3] palmitate and its low-molecular-weight metabolites in perfused rat livers is related to levels of L-FABP and not those of other intrahepatic proteins