Insulin-like growth factor binding protein-5 as a biomarker for detection of early liver disease

Study identifying an Insulin-like growth factor binding protein-5 as a biomarker for detection of early liver disease presented at the annual congress of the british toxicology societ

Ecological Impacts of the 2015/16 El Niño in the Central Equatorial Pacific

The authors thank Cisco Werner (NOAA/NMFS) for proposing this special issue and encouraging our submission. We thank each of the editors, Stephanie Herring, Peter Stott, and Nikos Christidis, for helpful guidance and support throughout the submittal process. We also thank each of the anonymous external reviewers for thoughtful guidance and suggestions to improve the manuscript. REB, TO, RV, AH, and BVA are grateful for support from the NOAA Coral Reef Conservation Program. AC acknowledges support from the National Science Foundation for the following awards: OCE 1537338, OCE 1605365, and OCE 1031971. This is PMEL contribution no. 4698. Any use of trade, firm, or product names is for descriptive purposes only and does not imply endorsement by the U.S. government. The views expressed in the article are not necessarily those of the U.S. government. (NOAA Coral Reef Conservation Program; OCE 1537338 - National Science Foundation; OCE 1605365 - National Science Foundation; OCE 1031971 - National Science Foundation

Increased postprandial glycaemia, insulinemia, and lipidemia after 10 weeks’ sucrose-rich diet compared to an artificially sweetened diet: a randomised controlled trial

The importance of exchanging sucrose for artificial sweeteners on risk factors for developing diabetes and cardiovascular diseases is not yet clear. Objective: To investigate the effects of a diet high in sucrose versus a diet high in artificial sweeteners on fasting and postprandial metabolic profiles after 10 weeks.Healthy overweight subjects were randomised to consume drinks and foods sweetened with either sucrose (∼2 g/kg body weight) (n = 12) or artificial sweeteners (n = 11) as supplements to their usual diet. Supplements were similar on the two diets and consisted of beverages (∼80 weight%) and solid foods (yoghurts, marmalade, ice cream, stewed fruits). The rest of the diet was free of choice and ad libitum. Before (week 0) and after the intervention (week 10) fasting blood samples were drawn and in week 10, postprandial blood was sampled during an 8-hour meal test (breakfast and lunch).After 10 weeks postprandial glucose, insulin, lactate, triglyceride, leptin, glucagon, and GLP-1 were all significantly higher in the sucrose compared with the sweetener group. After adjusting for differences in body weight changes and fasting values (week 10), postprandial glucose, lactate, insulin, GIP, and GLP-1 were significantly higher and after further adjusting for differences in energy and sucrose intake, postprandial lactate, insulin, GIP, and GLP-1 levels were still significantly higher on the sucrose-rich diet.A sucrose-rich diet consumed for 10 weeks resulted in significant elevations of postprandial glycaemia, insulinemia, and lipidemia compared to a diet rich in artificial sweeteners in slightly overweight healthy subjects

Pro-inflammatory flagellin proteins of prevalent motile commensal bacteria are variably abundant in the intestinal microbiome of elderly humans

Peer reviewedPublisher PD

Determinants of appetite ratings: the role of age, gender, BMI, physical activity, smoking habits, and diet/weight concern

Appetite measures are often recorded by visual analogue scales (VAS), and are assumed to reflect central nervous system (CNS) perceptions and sensations. However, little is known about how physiological, psychological, social, and cultural factors influence VAS.To investigate whether age, gender, body mass index (BMI), smoking habits, physical activity, diet behaviour, and menstruation cycle are determinants of appetite ratings.We investigated appetite ratings in different groups of a population during a single meal test, including 178 healthy women (98) and men (80), aged 20–60 years with a BMI of 18.5–35.0 kg/m2. Subjects consumed an evening meal composed to meet individual requirements of energy content and recommendations regarding macronutrient composition. Before and every half hour until 3 hours after the meal, subjects filled out VAS for satiety, fullness, hunger, and prospective food intake. They also filled in a questionnaire on eating/slimming behaviour.Multiple linear regression analyses showed that gender and age were the most powerful predictors of postprandial satiety (p<0.001, adj. R 2=0.19) and hunger (p<0.001, adj. R 2=0.15). Repeated measures general linear model (GLM) analyses revealed that women felt more satisfied than men (p<0.001) and older subjects felt more satisfied than younger (p<0.01). Furthermore, light/no exercisers felt more satisfied and less hungry than hard/moderate exercisers (p<0.05), but these differences disappeared after adjusting for age and gender. Smokers rated their prospective consumption lower than non-smokers (p < 005) and women in the ovulation phase felt less hungry than women in the menstruation phase (p<005). Neither BMI nor diet/weight concern were significantly associated with appetite ratings.Appetite ratings differed according to age, gender, and physical activity and to a lesser degree for smoking habits and menstruation cycle. Appetite ratings were not influenced by BMI and diet/weight concern. These factors should be considered when planning studies and analysing data concerning appetite sensations

Clinical Characteristics of a Non-Alcoholic Fatty Liver Disease Population Across the Fibrosis Spectrum Measured by Magnetic Resonance Elastography: Analysis of Screening Data

Introduction: Non-alcoholic fatty liver disease (NAFLD), one of the most common liver diseases, is associated with liver-related complications and metabolic comorbidities. The phenotype is wide, ranging from simple steatosis to non-alcoholic steatohepatitis with advanced fibrosis. In this analysis of a phase 1 trial, clinical characteristics of screened subjects with NAFLD were studied according to the extent of fibrosis assessed using magnetic resonance elastography (MRE). Methods: One hundred ninety-four subjects with body mass index (BMI) of 25–40\ua0kg/m2 and suspected NAFLD were assessed by MRE and grouped by MRE thresholds as a proxy for fibrosis staging (groups 0–4). Data were summarized by group levels, and correlation analyses between MRE values and clinical parameters (including magnetic resonance imaging-proton density fat fraction) were performed. Results: Most subjects had MRE values in the lower range (groups 0–1; N = 148). Type 2 diabetes (T2D) and BMI &gt; 35\ua0kg/m2 were more frequent in groups with higher than lower MRE values. Subjects in the highest MRE groups also tended to be older and have higher liver enzyme concentrations compared with lower MRE groups. No, or weak, correlations were found between MRE values and clinical parameters (all r values ≤ 0.45). Conclusions: There was considerable variation and overlap in clinical characteristics across the spectrum of liver stiffness. Although groups with high MRE values generally included more subjects with T2D and obesity, and had higher age and concentrations of liver enzymes, the clinical characteristics did not strongly correlate with MRE scores in this population. Trial Registration: Registered on Clinicaltrials.gov on November 29, 2017 (NCT03357380)

Microglia in Close Vicinity of Glioma Cells: Correlation Between Phenotype and Metabolic Alterations

Microglia are immune cells within the central nervous system. In brain-developing tumors, gliomas are able to silence the defense and immune functions of microglia, a phenomenon which strongly contributes to tumor progression and treatment resistance. Being activated and highly motile, microglia infiltrate tumors and secrete macrophagic chemoattractant factors. Thereafter, the tumor cells shut down their immune properties and stimulate the microglia to release tumor growth-promoting factors. The result of such modulation is that a kind of symbiosis occurs between microglia and tumor cells, in favor of tumor growth. However, little is known about microglial phenotype and metabolic modifications in a tumoral environment. Co-cultures were performed using CHME5 microglia cells grown on collagen beads or on coverslips and placed on monolayer of C6 cells, limiting cell/cell contacts. Phagocytic behavior and expression of macrophagic and cytoskeleton markers were monitored. Respiratory properties and energetic metabolism were also studied with regard to the activated phenotype of microglia. In co-cultures, transitory modifications of microglial morphology and metabolism were observed linked to a concomitant transitory increase of phagocytic properties. Therefore, after 1 h of co-culture, microglia were activated but when longer in contact with tumor cells, phagocytic properties appear silenced. Like the behavior of the phenotype, microglial respiration showed a transitory readjustment although the mitochondria maintained their perinuclear relocation. Nevertheless, the energetic metabolism of the microglia was altered, suggesting a new energetic steady state. The results clearly indicate that like the depressed immune properties, the macrophagic and metabolic status of the microglia is quickly driven by the glioma environment, despite short initial phagocytic activation. Such findings question the possible contribution of diffusible tumor factors to the microglial metabolism

Randomised clinical trial: Semaglutide versus placebo reduced liver steatosis but not liver stiffness in subjects with non-alcoholic fatty liver disease assessed by magnetic resonance imaging

Background: Glucagon-like peptide-1 receptor agonists may be a treatment option in patients with non-alcoholic fatty liver disease (NAFLD). Aims: To investigate the effects of semaglutide on liver stiffness and liver fat in subjects with NAFLD using non-invasive magnetic resonance imaging (MRI) methods. Methods: This randomised, double-blind, placebo-controlled trial enrolled subjects with liver stiffness 2.50-4.63\ua0kPa by magnetic resonance elastography (MRE) and liver steatosis ≥10% by MRI proton density fat fraction (MRI-PDFF). The primary endpoint was change from baseline to week 48 in liver stiffness assessed by MRE. Results: Sixty-seven subjects were randomised to once-daily subcutaneous semaglutide 0.4\ua0mg (n\ua0=\ua034) or placebo (n\ua0=\ua033). Change from baseline in liver stiffness was not significantly different between semaglutide and placebo at week 48 (estimated treatment ratio 0.96 (95% CI 0.89, 1.03; P\ua0=\ua00.2798); significant differences in liver stiffness were not observed at weeks 24 or 72. Reductions in liver steatosis were significantly greater with semaglutide (estimated treatment ratios: 0.70 [0.59, 0.84], P\ua0=\ua00.0002; 0.47 [0.36, 0.60], P\ua0&lt;\ua00.0001; and 0.50 [0.39, 0.66], P\ua0&lt;\ua00.0001) and more subjects achieved a\ua0≥\ua030% reduction in liver fat content with semaglutide at weeks 24, 48 and 72, (all P &lt; 0.001). Decreases in liver enzymes, body weight and HbA1c were also observed with semaglutide. Conclusions: The change in liver stiffness in subjects with NAFLD was not significantly different between semaglutide and placebo. However, semaglutide significantly reduced liver steatosis compared with placebo which, together with improvements in liver enzymes and metabolic parameters, suggests a positive impact on disease activity and metabolic profile