Adipokines 2.0

Once viewed solely as fat storage cells, adipocytes and their adipokines have now been proven to be central for human health. Understanding that overweight and obesity may increase the risk for various diseases requires detailed characterization of adipokine function. Weight gain, weight regain, and fasting affect adipocyte health and accordingly their secretome. Different adipose tissue deposits exist and they vary in cellular composition and function. The evidence is strong of a role of adipokines in cancer, reproductive function, neurological diseases, cardiovascular diseases ,and rheumatoid arthritis. Adipokines are considered useful biomarkers for adipose tissue and metabolic health, and may be used as diagnostic tools in rheumatoid arthritis, cancer, or sepsis. This book contains 10 original articles and 9 review articles focusing on these bioactive peptides. Several articles deal with chemerin, an adipokine discovered more than 20 years ago. Data so far have resulted in promising insights related to its biological function. We are only beginning to understand the multiple roles of chemerin, the mechanisms regulating its activity, and the signaling pathways used by this chemokine. Adipokine receptor agonists and antagonists may result in the formulation of novel drugs and ultimately may lead to new therapeutic targets to be used in clinical practice

High-resolution Visualization of Intestinal Microcirculation using Ultra-microangiography in Patients with Inflammatory Bowel Disease: A Pilot Study

Background & Aims: Ultra-microangiography (UMA) is a novel Doppler technique with optimized wall filtering that provides high sensitivity to low-velocity blood flows and optimized visualization of microcirculation. The aim of this pilot study was to compare intestinal vascularization assessed by color Doppler signals (CDS) and UMA. Methods: We investigated intestinal vascularization using UMA and CDS in 13 patients with confirmed inflammatory bowel disease (IBD). A cohort of 28 patients without structural bowel disease served as the control. Results: Microcirculation and dysregulated microcirculation in patients without and with inflammatory bowel disease can be visualized and quantified using UMA. In 83 % of IBD patients and 76% of non-IBD patients, a high resolution of intestinal perfusion could be achieved using UMA. Conclusions: To the best of our knowledge, this is the first study to investigate intestinal vascularization using UMA in patients with and without structural bowel disease. Quantification and visualization of intestinal vascularization should be further investigated in prospective studies and could help guide our therapy of patients with IBD

Chemokine-like receptor 1 mRNA weakly correlates with non-alcoholic steatohepatitis score in male but not female individuals

The chemokine-like receptor 1 (CMKLR1) ligands resolvin E1 and chemerin are known to modulate inflammatory response. The progression of non-alcoholic fatty liver disease (NAFLD) to non-alcoholic steatohepatitis (NASH) is associated with inflammation. Here it was analyzed whether hepatic CMKLR1 expression is related to histological features of NASH. Therefore, CMKLR1 mRNA was quantified in liver tissue of 33 patients without NAFLD, 47 patients with borderline NASH and 38 patients with NASH. Hepatic CMKLR1 mRNA was not associated with gender and body mass index (BMI) in the controls and the whole study group. CMKLR1 expression was similar in controls and in patients with borderline NASH and NASH. In male patients weak positive correlations with inflammation, fibrosis and NASH score were identified. In females CMKLR1 was not associated with features of NAFLD. Liver CMKLR1 mRNA tended to be higher in type 2 diabetes patients of both genders and in hypercholesterolemic women. In summary, this study shows that hepatic CMKLR1 mRNA is weakly associated with features of NASH in male patients only

Relevance in the Use of Appropriate Internal Standards for Accurate Quantification Using LC–MS/MS: Tauro-Conjugated Bile Acids as an Example

Compensation of matrix effects is the main obstacle to achieve accurate quantification in LC-MS/MS. Therefore, quantitative LC-MS/MS typically relies on addition of internal standards (ISs). Here, we present a systematic comparison of ISs from a routine LC-MS/MS method for bile acid (BA) analysis with a focus on tauro-conjugated. Both human serum based quality control (QC) and patient samples were quantified with a variety of stable isotope labeled (SIL) BAs including D-5-tauro BAs. As expected, SIL-ISs that match the endogenous analytes provide the highest data quality (precision, accuracy). We could not observe systematic correlation of data quality with chemical similarity or proximity in retention time of ISs to the analyte. However, both accuracy and precision of QCs and patient's concentrations showed significant correlation. This provides evidence that calculation of matrix-based QCs with various ISs could be applied for the selection of ISs whenever matching SILs are not available. Moreover, data calculated without ISs exhibited a poor data quality for both QCs and patients' concentrations. Considering these results, data generated without ISs should be interpreted with great care and may not be suitable for proposal of biomarkers unless solid quantitative data could confirm initial findings

Linguistic, social, and individual factors constraining variation in spoken Swiss Standard German

This chapter explores linguistic, social, and individual factors constraining spoken Swiss Standard German. The empirical focus of this study is on the variables (k) and (ç), which are well-attested to vary both at the level of the Swiss German speech community as a whole and also at the level of individual speakers within the community. Our data are based on sociolinguistic interviews including informal conversations (comprehension-oriented) as well as reading and transla- tion tasks (norm-oriented) from 16 adults ranging in age from 19 to 40 who were born and work in the city of Biel in North-West Switzerland. Results show that level of education and gender explain most of the variation present in the data, despite these factors not affecting (k) and (ç) equally. Language internal constraints only play a minor role. However, no systematic stylistic variation was found regarding the communicative orientation of the different language production tasks. Based on these findings, this chapter furthermore addresses theoretical and methodological questions regarding systematic and non-systematic variation within individuals. In particular with respect to the results found at the level of the individual, it needs to be questioned whether (social) factors determining variation based on group averages can be generalised to individuals’ behaviour. Hence, we argue in this chapter that variationist sociolinguists should be more careful when it comes to drawing inferences based on group-derived estimates only. Keywords: Spoken Swiss Standard German, Variationist Sociolinguistics, Intra- individual Variation, Inter-individual Variation, Linguistic and Social Factor

Lipidomic analysis of serum from high-fat diet induced obese mice

Lipid metabolites regulate fatty acid and glucose homeostasis. The intention of the current study is to identify circulating lipid species, which are altered in rodent obesity and strongly correlate with the classically measured metabolites glucose, triglycerides, and cholesterol. Mice fed a high fat diet (HFD) for 14 weeks have increased body weight and fasting glucose. Serum triglycerides are not altered, while cholesterol tends to be increased. Accordingly, major cholesteryl ester (CE) species and free cholesterol are not significantly raised in obesity while minor metabolites, including CE 20:3 and CE 18:3, are increased or reduced, respectively. Distinct sphingomyelin (SM) species are elevated while ceramides are not raised. Phosphatidylinositol (PI) species, including PI 34:1, are raised while others are decreased. PI 34:1 strongly correlates with fasting glucose and proinsulin levels. Phosphatidylcholine (PC) 26:0, 40:2, and 40:5, which are induced in obesity, correlate with cholesterol. PC 38:4 and PC 40:6 are also raised in fat fed mice and positively correlate with fasting glucose. Lysophosphatidylcholine (LPC) species are also changed in obesity and the already shown reduction of LPC 16:1 has been confirmed. LPC 22:4, which is increased, correlates with serum cholesterol. The data indicate that circulating levels of various lipid species are changed in the obesity model studied and some of them are strongly associated with classically measured metabolites