Plasma acylcarnitine concentrations reflect the acylcarnitine profile in cardiac tissues

Funding Information: This study was supported by the Latvian National Research Program BIOMEDICINE. E. Liepinsh was supported by the FP7 project InnovaBalt [grant Nr. 316149]. We would like to thank Dr. Reinis Vilskersts and Gita Dambrova for help with the isolated skeletal muscle experiments. Publisher Copyright: © 2017 The Author(s).Increased plasma concentrations of acylcarnitines (ACs) are suggested as a marker of metabolism disorders. The aim of the present study was to clarify which tissues are responsible for changes in the AC pool in plasma. The concentrations of medium- and long-chain ACs were changing during the fed-fast cycle in rat heart, muscles and liver. After 60 min running exercise, AC content was increased in fasted mice muscles, but not in plasma or heart. After glucose bolus administration in fasted rats, the AC concentrations in plasma decreased after 30 min but then began to increase, while in the muscles and liver, the contents of medium- and long-chain ACs were unchanged or even increased. Only the heart showed a decrease in medium- and long-chain AC contents that was similar to that observed in plasma. In isolated rat heart, but not isolated-contracting mice muscles, the significant efflux of medium- and long-chain ACs was observed. The efflux was reduced by 40% after the addition of glucose and insulin to the perfusion solution. Overall, these results indicate that during fed-fast cycle shifting the heart determines the medium- and long-chain AC profile in plasma, due to a rapid response to the availability of circulating energy substrates.publishersversionPeer reviewe

A data integration multi-omics approach to study calorie restriction-induced changes in insulin sensitivity

Background: The mechanisms responsible for calorie restriction-induced improvement in insulin sensitivity have not been fully elucidated. Greater insight can be achieved through deep biological phenotyping of subjects undergoing calorie restriction, and integration of big data. Materials and Methods: An integrative approach was applied to investigate associations between change in insulin sensitivity and factors from host, microbiota and lifestyle after a 6-week calorie restriction period in 27 overweight or obese adults (ClinicalTrials.gov: NCT01314690). Partial least squares regression was used to determine associations of change (week 6 – baseline) between insulin sensitivity markers and lifestyle factors (diet and physical activity), subcutaneous adipose tissue (sAT) gene expression, metabolomics in serum, urine and feces, and gut microbiota composition. ScaleNet, a network learning approach based on spectral consensus strategy (SCS, developed by us) was used for reconstruction of biological networks. Results: A spectrum of variables from lifestyle factors (10 nutrients), gut microbiota (10 metagenomics species) and host multi-omics (metabolic features: 84 from serum, 73 from urine, and 131 from feces; and 257 subcutaneous adipose tissue gene probes) most associated with insulin sensitivity were identified. Biological network reconstruction using SCS, highlighted links between changes in insulin sensitivity, serum branched chain amino acids, sAT genes involved in endoplasmic reticulum stress and ubiquitination, and gut metagenomic species. Linear regression analysis to model how changes of select variables over the calorie restriction period contribute to changes in insulin sensitivity, showed greatest contributions from gut metagenomic species and fiber intake. Conclusions: This work has enhanced previous knowledge on links between host glucose homeostasis, lifestyle factors and microbiota, and has identified potential biomarkers that may be used in future studies to predict and improve individual response to weight-loss interventions. Furthermore, this is the first study showing integration of the wide range of data presented herein, identifying 115 variables of interest with respect to insulin sensitivity from the initial input, consisting of 9,986 variables

Here, there and everywhere. A multi organ approach to acylcarnitine metabolism

In this thesis, we investigated acylcarnitines in plasma and insulin sensitive tissues in fasted, fed and a high fat diet (HFD)-induced, insulin resistant state. Acylcarnitines are fatty acid oxidation intermediates. They comprise of a fatty acid bound to carnitine, so that the fatty acid can enter the otherwise impermeable mitochondrion for oxidation purposes. By studying acylcarnitine concentrations, kinetics, and fluxes, we aimed to understand whole body acylcarnitine metabolism under different metabolic circumstances, including pathological conditions such as insulin resistance characterized by derangements in acylcarnitine profiles

Evaluation of Platelet Concentrates with the New Dideco Blood Cell Separator: Excel

The Excel Cell Separator produced by Dideco represents a good compromise between automation and Platelet efficiency. Platelet activation is a phenomenon that we can find with the concentrates of all cell separators. Although, the complement activation of Excel is extremely lower in comparison with the same data obtained using all the other cell separators, the 5-day storage is acceptable. It will be important to research the bacteriological controls. Like the pH of the platelet bags, because in certain cases it was too low. For the future it will be interesting to study the possibility to predict the quantity of platelets collected having a system that is adaptable with the donor parameters. </jats:p