Circulating metabolites in progression to islet autoimmunity and type 1 diabetes

Aims/hypothesis Metabolic dysregulation may precede the onset of type 1 diabetes. However, these metabolic disturbances and their specific role in disease initiation remain poorly understood. In this study, we examined whether children who progress to type 1 diabetes have a circulatory polar metabolite profile distinct from that of children who later progress to islet autoimmunity but not type 1 diabetes and a matched control group. Methods We analysed polar metabolites from 415 longitudinal plasma samples in a prospective cohort of children in three study groups: those who progressed to type 1 diabetes; those who seroconverted to one islet autoantibody but not to type 1 diabetes; and an antibody-negative control group. Metabolites were measured using two-dimensional GC high-speed time of flight MS. Results In early infancy, progression to type 1 diabetes was associated with downregulated amino acids, sugar derivatives and fatty acids, including catabolites of microbial origin, compared with the control group. Methionine remained persistently upregulated in those progressing to type 1 diabetes compared with the control group and those who seroconverted to one islet autoantibody. The appearance of islet autoantibodies was associated with decreased glutamic and aspartic acids. Conclusions/interpretation Our findings suggest that children who progress to type 1 diabetes have a unique metabolic profile, which is, however, altered with the appearance of islet autoantibodies. Our findings may assist with early prediction of the disease.Peer reviewe

Pinot Noir grape colour related phenolics as affected by leaf removal treatments in the Vipava Valley

Wine colour depends directly on the quantitative and qualitative profiles of anthocyanins, flavonols and hydroxycinnamic acids, as well as on their involvement in polymerization and co-pigmentation reactions. Pinot Noir is a grape variety with a low natural colour potential, often combined with problems of low colour stability for its wines during aging. The influence of leaf removal timing on grape colour related polyphenols was observed during maturation and at harvest time for the 2009 vintage \u2018\u2018real scenario\u2019\u2019 conditions in two different vineyards in the Vipava Valley (Slovenia), known for its warm but windy climate. With different timing of leaf removal, a different microclimate can be achieved, with different light exposure for the specific plant tissue and different temperatures on berry surfaces. Phenolic compounds were characterised and quantified using HPLC/Vis. Three classes of polyphenols were affected by leaf removal timing, but with differing intensities and with some differences between locations. Hydroxycinnamic acids were affected only slightly, mostly at the beginning of the maturation period. Anthocyanins were significantly affected, while flavonols were the most affected by treatments in both vineyards and their concentration was clearly related to modification of the light within the canopy

Effects of Temperature and Photoperiod on Yield and Chemical Composition of Northern and Southern Clones of Bilberry (Vaccinium myrtillus L.)

After pollination outdoors individual bilberry plants from two Northern and two Southern clones were studied for climatic effects on berry yield and quality in a controlled phytotrone experiment at 12 °C and 18 °C. At each temperature the following light treatments were tested; 1) 12 h natural light; 2) 24 h natural light and 3) 24 h natural light plus red light. The first experimental year there was no difference in yield between temperatures, however, the second experimental year the berry yields was significantly higher at 18 °C. Berry ripening was faster in the Northern than in the Southern clones at 12 °C. Northern clones also showed significantly higher contents of total anthocyanins, all measured anthocyanin derivatives, total phenolics, malic acid and sucrose. Metabolic profiling revealed higher levels of flavanols, hydroxycinnamic acids, quinic acid and carbohydrates at 12 °C

Effects of Temperature and Photoperiod on Yield and Chemical Composition of Northern and Southern Clones of Bilberry (Vaccinium myrtillus L.)

After pollination outdoors individual bilberry plants from two Northern and two Southern clones were studied for climatic effects on berry yield and quality in a controlled phytotrone experiment at 12 °C and 18 °C. At each temperature the following light treatments were tested; 1) 12 h natural light; 2) 24 h natural light and 3) 24 h natural light plus red light. The first experimental year there was no difference in yield between temperatures, however, the second experimental year the berry yields was significantly higher at 18 °C. Berry ripening was faster in the Northern than in the Southern clones at 12 °C. Northern clones also showed significantly higher contents of total anthocyanins, all measured anthocyanin derivatives, total phenolics, malic acid and sucrose. Metabolic profiling revealed higher levels of flavanols, hydroxycinnamic acids, quinic acid and carbohydrates at 12 °C

Intravenous nicotinamide riboside elevates mouse skeletal muscle NAD⁺ without impacting respiratory capacity or insulin sensitivity

In clinical trials, oral supplementation with nicotinamide riboside (NR) fails to increase muscle mitochondrial respiratory capacity and insulin sensitivity but also does not increase muscle NAD(+) levels. This study tests the feasibility of chronically elevating skeletal muscle NAD(+) in mice and investigates the putative effects on mitochondrial respiratory capacity, insulin sensitivity, and gene expression. Accordingly, to improve bioavailability to skeletal muscle, we developed an experimental model for administering NR repeatedly through a jugular vein catheter. Mice on a Western diet were treated with various combinations of NR, pterostilbene (PT), and voluntary wheel running, but the metabolic effects of NR and PT treatment were modest. We conclude that the chronic elevation of skeletal muscle NAD(+) by the intravenous injection of NR is possible but does not affect muscle respiratory capacity or insulin sensitivity in either sedentary or physically active mice. Our data have implications for NAD(+) precursor supplementation regimens

Use of non-conventional yeast improves the wine aroma profile of Ribolla Gialla

Consumer wine preferences are changing rapidly towards exotic flavours and tastes. In this work, we tested five non-conventional yeast strains for their potential to improve Ribolla Gialla wine quality. These strains were previously selected from numerous yeasts interesting as food production candidates. Sequential fermentation of Ribolla Gialla grape juice with the addition of the Saccharomyces cerevisiae T73 Lalvin industrial strain was performed. Zygosaccharomyces kombuchaensis CBS8849 and Kazachstania gamospora CBS10400 demonstrated positive organoleptic properties and suitable fermentation dynamics, rapid sugar consumption and industrial strain compatibility. At the same time, Torulaspora microellipsoides CBS6641, Dekkera bruxellensis CBS2796 and Dekkera anomala CBS77 were unsuitable for wine production because of poor fermentation dynamics, inefficient sugar consumption and ethanol production levels and major organoleptic defects. Thus, we selected strains of K. gamospora and Z. kombuchaensis that significantly improved the usually plain taste of Ribolla wine by providing additional aromatic complexity in a controlled and reproducible manne

Lipidomics of human adipose tissue reveals diversity between body areas

Background and aimsAdipose tissue plays a pivotal role in storing excess fat and its composition reflects the history of person's lifestyle and metabolic health. Broad profiling of lipids with mass spectrometry has potential for uncovering new knowledge on the pathology of obesity, metabolic syndrome, diabetes and other related conditions. Here, we developed a lipidomic method for analyzing human subcutaneous adipose biopsies. We applied the method to four body areas to understand the differences in lipid composition between these areas.Materials and methodsAdipose tissue biopsies from 10 participants were analyzed using ultra-high-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry. The sample preparation optimization included the optimization of the lipid extraction, the sample amount and the sample dilution factor to detect lipids in an appropriate concentration range. Lipidomic analyses were performed for adipose tissue collected from the abdomen, breast, thigh and lower back. Differences in lipid levels between tissues were visualized with heatmaps.ResultsLipidomic analysis on human adipose biopsies lead to the identification of 186lipids in 2 mg of sample. Technical variation of the lipid-class specific internal standards were below 5%, thus indicating acceptable repeatability. Triacylglycerols were highly represented in the adipose tissue samples, and lipids from 13 lipid classes were identified. Long polyunsaturated triacylglycerols in higher levels in thigh (qConclusionThe method presented here is suitable for the analysis of lipid profiles in 2 mg of adipose tissue. The amount of fat across the body is important for health but we argue that also the distribution and the particular profile of the lipidome may be relevant for metabolic outcomes. We suggest that the method presented in this paper could be useful for detecting such aberrations

Comprehensive lipidomics reveals phenotypic differences in hepatic lipid turnover in ALD and NAFLD during alcohol intoxication

BACKGROUND & AIMS: In experimental models, alcohol induces acute changes in lipid metabolism that cause hepatocyte lipoapoptosis and inflammation. Here we study human hepatic lipid turnover during controlled alcohol intoxication. METHODS: We studied 39 participants with 3 distinct hepatic phenotypes: alcohol-related liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), and healthy controls. Alcohol was administrated via nasogastric tube over 30 min. Hepatic and systemic venous blood was sampled simultaneously at 3 time points: baseline, 60, and 180 min after alcohol intervention. Liver biopsies were sampled 240 min after alcohol intervention. We used ultra-high performance liquid chromatography mass spectrometry to measure levels of more than 250 lipid species from the blood and liver samples. RESULTS: After alcohol intervention, the levels of blood free fatty acid (FFA) and lysophosphatidylcholine (LPC) decreased, while triglyceride (TG) increased. FFA was the only lipid class to decrease in NAFLD after alcohol intervention, whereas LPC and FFA decreased and TG increased after intervention in ALD and healthy controls. Fatty acid chain uptake preference in FFAs and LPCs were oleic acid, linoleic acid, arachidonic acid, and docosahexaenoic acid. Hepatic venous blood FFA and LPC levels were lower when compared with systemic venous blood levels throughout the intervention. After alcohol intoxication, liver lipidome in ALD was similar to that in NAFLD. CONCLUSIONS: Alcohol intoxication induces rapid changes in circulating lipids including hepatic turnaround from FFA and LPC, potentially leading to lipoapoptosis and steatohepatitis. TG clearance was suppressed in NAFLD, possibly explaining why alcohol and NAFLD are synergistic risk factors for disease progression. These effects may be central to the pathogenesis of ALD. CLINICAL TRIALS REGISTRATION: The study is registered at Clinicaltrials.gov (NCT03018990). LAY SUMMARY: We report that alcohol induces hepatic extraction of free unsaturated fatty acids and lysophosphatidylcholines, hepatotoxic lipids which have not been previously associated with alcohol-induced liver injury. We also found that individuals with non-alcoholic fatty liver disease have reduced lipid turnover during alcohol intoxication when compared with people with alcohol-related fatty liver disease. This may explain why alcohol is particularly more harmful in people with non-alcoholic fatty liver and why elevated BMI and alcohol have a synergistic effect on the risk of liver-related death