Serum levels of interleukin-22, cardiometabolic risk factors and incident type 2 diabetes: KORA F4/FF4 study

AIMS: Interleukin-22 (IL-22) has beneficial effects on body weight, insulin resistance and inflammation in different mouse models, but its relevance for the development of type 2 diabetes in humans is unknown. We aimed to identify correlates of serum IL-22 levels and to test the hypothesis that higher IL-22 levels are associated with lower diabetes incidence. METHODS: Cross-sectional associations between serum IL-22, cardiometabolic risk factors and glucose tolerance status were investigated in 1107 persons of the population-based KORA F4 study. The prospective association between serum IL-22 and incident type 2 diabetes was assessed in 504 initially non-diabetic study participants in both the KORA F4 study and its 7-year follow-up examination KORA FF4, 76 of whom developed diabetes. RESULTS: Male sex, current smoking, lower HDL cholesterol, lower estimated glomerular filtration rate and higher serum interleukin-1 receptor antagonist were associated with higher IL-22 levels after adjustment for confounders (all P < 0.05). Serum IL-22 showed no associations with glucose tolerance status, prediabetes or type 2 diabetes. Baseline serum IL-22 levels (median, 25th/75th percentiles) for incident type 2 diabetes cases and non-cases were 6.28 (1.95; 12.35) and 6.45 (1.95; 11.80) pg/ml, respectively (age and sex-adjusted P = 0.744). The age and sex-adjusted OR (95% CI) per doubling of IL-22 for incident type 2 diabetes of 1.02 (0.85; 1.23) was almost unchanged after consideration of further confounders. CONCLUSIONS: High serum levels of IL-22 were positively rather than inversely associated with several cardiometabolic risk factors. However, these associations did not translate into an increased risk for type 2 diabetes. Thus, our data argue against the utility of IL-22 as biomarker for prevalent or incident type 2 diabetes in humans, but identify potential determinants of IL-22 levels which merits further research in the context of cardiovascular diseases

Origin and fate of dissolved organic matter in four shallow Baltic Sea estuaries

Coastal waters have strong gradients in dissolved organic matter (DOM) quantity and characteristics, originating from terrestrial inputs and autochthonous production. Enclosed seas with high freshwater input therefore experience high DOM concentrations and gradients from freshwater sources to more saline waters. The brackish Baltic Sea experiences such salinity gradients from east to west and from river mouths to the open sea. Furthermore, the catchment areas of the Baltic Sea are very diverse and vary from sparsely populated northern areas to densely populated southern zones. Coastal systems vary from enclosed or open bays, estuaries, fjords, archipelagos and lagoons where the residence time of DOM at these sites varies and may control the extent to which organic matter is biologically, chemically or physically modified or simply diluted with transport off-shore. Data of DOM with simultaneous measurements of dissolved organic (DO) nitrogen (N), carbon (C) and phosphorus (P) across a range of contrasting coastal systems are scarce. Here we present data from the Roskilde Fjord, Vistula and Öre estuaries and Curonian Lagoon; four coastal systems with large differences in salinity, nutrient concentrations, freshwater inflow and catchment characteristics. The C:N:P ratios of DOM of our data, despite high variability, show site specific significant differences resulting largely from differences residence time. Microbial processes seemed to have minor effects, and only in spring did uptake of DON in the Vistula and Öre estuaries take place and not at the other sites or seasons. Resuspension from sediments impacts bottom waters and the entire shallow water column in the Curonian Lagoon. Finally, our data combined with published data show that land use in the catchments seems to impact the DOC:DON and DOC:DOP ratios of the tributaries most.peerReviewe

Linking process rates with modelling data and ecosystem characteristics

This report is related to the BONUS project “Nutrient Cocktails in COAstal zones of the Baltic Sea” alias COCOA. The aim of BONUS COCOA is to investigate physical, biogeochemical and biological processes in a combined and coordinated fashion to improve the understanding of the interaction of these processes on the removal of nutrients along the land-sea interface. The report is especially related to BONUS COCOA WP 6 in which the main objective is extrapolation of results from the BONUS COCOA learning sites to coastal sites around the Baltic Sea in general. Specific objectives of this deliverable (D6.4) were to connect observed process rates with modelling data and ecosystem characteristics. In the report we made statistical analyses of observations from BONUS COCOA study sites together with results from the Swedish Coastal zone Model (SCM). Eight structural variables (water depth, temperature, salinity, bottom water concentrations of oxygen, ammonium, nitrate and phosphate, as well as nitrogen content in sediment) were found common to both the experimentally determined and the model data sets. The observed process rate evaluated in this report was denitrification. In addition regressions were tested between observed denitrification rates and several structural variables (latitude, longitude, depth, light, temperature, salinity, grain class, porosity, loss of ignition, sediment organic carbon, total nitrogen content in the sediment,  sediment carbon/nitrogen-ratio, sediment chlorphyll-a as well as bottom water concentrations of oxygen, ammonium, nitrate, and dissolved inorganic  phosphorus and silicate) for pooled data from all learning sites. The statistical results showed that experimentally determined multivariate data set from the shallow, illuminated stations was mainly found to be similar to the multivariate data set produced by the SCM model. Generally, no strong correlations of simple relations between observed denitrification and available structural variables were found for data collected from all the learning sites. We found some non-significant correlation between denitrification rates and bottom water dissolved inorganic phosphorous and dissolved silica but the reason behind the correlations is not clear. We also developed and evaluated a theory to relate process rates to monitoring data and nutrient retention. The theoretical analysis included nutrient retention due to denitrification as well as burial of phosphorus and nitrogen. The theory of nutrient retention showed good correlations with model results. It was found that area-specific nitrogen and phosphorus retention capacity in a sub-basin depend much on mean water depth, water residence time, basin area and the mean nutrient concentrations in the active sediment layer and in the water column

Factors regulating the coastal nutrient filter in the Baltic Sea

The coastal zone of the Baltic Sea is diverse with strong regional differences in the physico-chemical setting. This diversity is also reflected in the importance of different biogeochemical processes altering nutrient and organic matter fluxes on the passage from land to sea. This review investigates the most important processes for removal of nutrients and organic matter, and the factors that regulate the efficiency of the coastal filter. Nitrogen removal through denitrification is high in lagoons receiving large inputs of nitrate and organic matter. Phosphorus burial is high in archipelagos with substantial sedimentation, but the stability of different burial forms varies across the Baltic Sea. Organic matter processes are tightly linked to the nitrogen and phosphorus cycles. Moreover, these processes are strongly modulated depending on composition of vegetation and fauna. Managing coastal ecosystems to improve the effectiveness of the coastal filter can reduce eutrophication in the open Baltic Sea.peerReviewe

Hypoxia in the Baltic Sea: Biogeochemical cycles, benthic fauna, and management

Open Access-maksut maksettu/Tutkijan ilmoitusPeer reviewe

Multi-omic signature of body weight change: results from a population-based cohort study

BACKGROUND: Excess body weight is a major risk factor for cardiometabolic diseases. The complex molecular mechanisms of body weight change-induced metabolic perturbations are not fully understood. Specifically, in-depth molecular characterization of long-term body weight change in the general population is lacking. Here, we pursued a multi-omic approach to comprehensively study metabolic consequences of body weight change during a seven-year follow-up in a large prospective study. METHODS: We used data from the population-based Cooperative Health Research in the Region of Augsburg (KORA) S4/F4 cohort. At follow-up (F4), two-platform serum metabolomics and whole blood gene expression measurements were obtained for 1,631 and 689 participants, respectively. Using weighted correlation network analysis, omics data were clustered into modules of closely connected molecules, followed by the formation of a partial correlation network from the modules. Association of the omics modules with previous annual percentage weight change was then determined using linear models. In addition, we performed pathway enrichment analyses, stability analyses, and assessed the relation of the omics modules with clinical traits. RESULTS: Four metabolite and two gene expression modules were significantly and stably associated with body weight change (P-values ranging from 1.9 × 10−4 to 1.2 × 10−24). The four metabolite modules covered major branches of metabolism, with VLDL, LDL and large HDL subclasses, triglycerides, branched-chain amino acids and markers of energy metabolism among the main representative molecules. One gene expression module suggests a role of weight change in red blood cell development. The other gene expression module largely overlaps with the lipid-leukocyte (LL) module previously reported to interact with serum metabolites, for which we identify additional co-expressed genes. The omics modules were interrelated and showed cross-sectional associations with clinical traits. Moreover, weight gain and weight loss showed largely opposing associations with the omics modules. CONCLUSIONS: Long-term weight change in the general population globally associates with serum metabolite concentrations. An integrated metabolomics and transcriptomics approach improved the understanding of molecular mechanisms underlying the association of weight gain with changes in lipid and amino acid metabolism, insulin sensitivity, mitochondrial function as well as blood cell development and function

Extensive alterations of the whole-blood transcriptome are associated with body mass index: results of an mRNA profiling study involving two large population-based cohorts

Background: Obesity, defined as pathologically increased body mass index (BMI),is strongly related to an increased risk for numerous common cardiovascular and metabolic diseases. It is particularly associated with insulin resistance, hyperglycemia, and systemic oxidative stress and represents the most important risk factor for type 2 diabetes (T2D). However, the pathophysiological mechanisms underlying these associations are still not completely understood. Therefore, in order to identify potentially disease-relevant BMI-associated gene expression signatures, a transcriptome-wide association study (TWAS) on BMI was performed. Methods: Whole-blood mRNA levels determined by array-based transcriptional profiling were correlated with BMI in two large independent population-based cohort studies (KORA F4 and SHIP-TREND) comprising a total of 1977 individuals. Results: Extensive alterations of the whole-blood transcriptome were associated with BMI: More than 3500 transcripts exhibited significant positive or negative BMI-correlation. Three major whole-blood gene expression signatures associated with increased BMI were identified. The three signatures suggested: i) a ratio shift from mature erythrocytes towards reticulocytes, ii) decreased expression of several genes essentially involved in the transmission and amplification of the insulin signal, and iii) reduced expression of several key genes involved in the defence against reactive oxygen species (ROS). Conclusions: Whereas the first signature confirms published results, the other two provide possible mechanistic explanations for well-known epidemiological findings under conditions of increased BMI, namely attenuated insulin signaling and increased oxidative stress. The putatively causative BMI-dependent down-regulation of the expression of numerous genes on the mRNA level represents a novel finding. BMI-associated negative transcriptional regulation of insulin signaling and oxidative stress management provide new insights into the pathogenesis of metabolic syndrome and T2D

A meta-analysis of gene expression signatures of blood pressure and hypertension.

Genome-wide association studies (GWAS) have uncovered numerous genetic variants (SNPs) that are associated with blood pressure (BP). Genetic variants may lead to BP changes by acting on intermediate molecular phenotypes such as coded protein sequence or gene expression, which in turn affect BP variability. Therefore, characterizing genes whose expression is associated with BP may reveal cellular processes involved in BP regulation and uncover how transcripts mediate genetic and environmental effects on BP variability. A meta-analysis of results from six studies of global gene expression profiles of BP and hypertension in whole blood was performed in 7017 individuals who were not receiving antihypertensive drug treatment. We identified 34 genes that were differentially expressed in relation to BP (Bonferroni-corrected p<0.05). Among these genes, FOS and PTGS2 have been previously reported to be involved in BP-related processes; the others are novel. The top BP signature genes in aggregate explain 5%-9% of inter-individual variance in BP. Of note, rs3184504 in SH2B3, which was also reported in GWAS to be associated with BP, was found to be a trans regulator of the expression of 6 of the transcripts we found to be associated with BP (FOS, MYADM, PP1R15A, TAGAP, S100A10, and FGBP2). Gene set enrichment analysis suggested that the BP-related global gene expression changes include genes involved in inflammatory response and apoptosis pathways. Our study provides new insights into molecular mechanisms underlying BP regulation, and suggests novel transcriptomic markers for the treatment and prevention of hypertension

A meta-analysis of gene expression signatures of blood pressure and hypertension

Genome-wide association studies (GWAS) have uncovered numerous genetic variants (SNPs) that are associated with blood pressure (BP). Genetic variants may lead to BP changes by acting on intermediate molecular phenotypes such as coded protein sequence or gene expression, which in turn affect BP variability. Therefore, characterizing genes whose expression is associated with BP may reveal cellular processes involved in BP regulation and uncover how transcripts mediate genetic and environmental effects on BP variability. A meta-analysis of results from six studies of global gene expression profiles of BP and hypertension in whole blood was performed in 7017 individuals who were not receiving antihypertensive drug treatment. We identified 34 genes that were differentially expressed in relation to BP (Bonferroni-corrected p<0.05). Among these genes, FOS and PTGS2 have been previously reported to be involved in BP-related processes; the others are novel. The top BP signature genes in aggregate explain 5%-9% of inter-individual variance in BP. Of note, rs3184504 in SH2B3, which was also reported in GWAS to be associated with BP, was found to be a trans regulator of the expression of 6 of the transcripts we found to be associated with BP (FOS, MYADM, PP1R15A, TAGAP, S100A10, and FGBP2). Gene set enrichment analysis suggested that the BP-related global gene expression changes include genes involved in inflammatory response and apoptosis pathways. Our study provides new insights into molecular mechanisms underlying BP regulation, and suggests novel transcriptomic markers for the treatment and prevention of hypertension

Transcript profiling of candidate genes in testis of pigs exhibiting large differences in androstenone levels

<p>Abstract</p> <p>Background</p> <p>Boar taint is an unpleasant odor and flavor of the meat and occurs in a high proportion of uncastrated male pigs. Androstenone, a steroid produced in testis and acting as a sex pheromone regulating reproductive function in female pigs, is one of the main compounds responsible for boar taint. The primary goal of the present investigation was to determine the differential gene expression of selected candidate genes related to levels of androstenone in pigs.</p> <p>Results</p> <p>Altogether 2560 boars from the Norwegian Landrace and Duroc populations were included in this study. Testicle samples from the 192 boars with most extreme high or low levels of androstenone in fat were used for RNA extraction, and 15 candidate genes were selected and analyzed by real-competitive PCR analysis. The genes Cytochrome P450 c17 (<it>CYP17A1</it>), Steroidogenic acute regulatory protein (<it>STAR</it>), Aldo-keto reductase family 1 member C4 (<it>AKR1C4</it>), Short-chain dehydrogenase/reductase family member 4 (<it>DHRS4</it>), Ferritin light polypeptide (<it>FTL</it>), Sulfotransferase family 2A, dehydroepiandrosterone-preferring member 1 (<it>SULT2A1</it>), Cytochrome P450 subfamily XIA polypeptide 1 (<it>CYP11A1</it>), Cytochrome b5 (<it>CYB5A</it>), and 17-beta-Hydroxysteroid dehydrogenase IV (<it>HSD17B4</it>) were all found to be significantly (P < 0.05) up-regulated in high androstenone boars in both Duroc and Landrace. Furthermore, Cytochrome P450 c19A2 (<it>CYP19A2</it>) was down-regulated and progesterone receptor membrane component 1 (<it>PGRMC1</it>) was up-regulated in high-androstenone Duroc boars only, while <it>CYP21 </it>was significantly down-regulated (2.5) in high-androstenone Landrace only. The genes Nuclear Receptor co-activator 4 (<it>NCOA4</it>), Sphingomyrlin phosphodiesterase 1 (<it>SMPD1</it>) and 3β-hydroxysteroid dehydrogenase (<it>HSD3B</it>) were not significantly differentially expressed in any breeds. Additionally, association studies were performed for the genes with one or more detected SNPs. Association between SNP and androstenone level was observed in <it>CYB5A </it>only, suggesting cis-regulation of the differential transcription in this gene.</p> <p>Conclusion</p> <p>A large pig material of highly extreme androstenone levels is investigated. The current study contributes to the knowledge about which genes that is differentially expressed regard to the levels of androstenone in pigs. Results in this paper suggest that several genes are important in the regulation of androstenone level in boars and warrant further evaluation of the above mentioned candidate genes, including analyses in different breeds, identification of causal mutations and possible gene interactions.</p