Background Succinate is produced by both host and microbiota, with a key role in the interplay of immunity and metabolism and an emerging role as a biomarker for inflammatory and metabolic... Show moreBackground Succinate is produced by both host and microbiota, with a key role in the interplay of immunity and metabolism and an emerging role as a biomarker for inflammatory and metabolic disorders in middle-aged adults. The relationship between plasma succinate levels and cardiovascular disease (CVD) risk in young adults is unknown.MethodsCross-sectional study in 100 (65% women) individuals aged 18-25 years from the ACTIvating Brown Adipose Tissue through Exercise (ACTIBATE) study cohort. CVD risk factors, body composition, dietary intake, basal metabolic rate, and cardiorespiratory fitness were assessed by routine methods. Plasma succinate was measured with an enzyme-based assay. Brown adipose tissue (BAT) was evaluated by positron emission tomography, and circulating oxylipins were assessed by targeted metabolomics. Fecal microbiota composition was analyzed in a sub-sample.ResultsIndividuals with higher succinate levels had higher levels of visceral adipose tissue (VAT) mass (+42.5%), triglycerides (+63.9%), C-reactive protein (+124.2%), diastolic blood pressure (+5.5%), and pro-inflammatory omega-6 oxylipins than individuals with lower succinate levels. Succinate levels were also higher in metabolically unhealthy individuals than in healthy overweight/obese peers. Succinate levels were not associated with BAT volume or activity or with fecal microbiota composition and diversity.ConclusionsPlasma succinate levels are linked to a specific pro-inflammatory omega-6 signature pattern and higher VAT levels, and seem to reflect the cardiovascular status of young adults. Show less
In order to gain a better insight into the basis of the rapid jasmonic acid (JA)-mediated stress response, an integrated approach using a targeted high-resolution mass spectrometry-based (HRMS)... Show moreIn order to gain a better insight into the basis of the rapid jasmonic acid (JA)-mediated stress response, an integrated approach using a targeted high-resolution mass spectrometry-based (HRMS) platform, was conducted to monitor the metabolism of JA using the model system of cell suspension cultures of Catharanthus roseus. Components in the JA-pathway involved in the primary metabolism such as the fatty acid (FA)-precursor C18:3; terpenoid indole alkaloids (TIA) belonging to the secondary metabolism and JA derivatives involved in its catabolism were examined. The effects of JA on FA and TIA in cell suspension cultures of C. roseus were time dependent and are thus considered late events in the JA-stress response. Feeding cells with d5-dnOPDA led to the accumulation of d5-JA and d5-JA-Ile in cells, proving that cells are constitutively ready to incorporate and transform dnOPDA into JA-Ile catalyzed by JA-amino synthetase 1 (JAR1). Moreover, d5-JA was excreted to the growth medium possibly by JA/JA-Ile TRANSPORTER 1 (JAT1). Signal attenuation of JA included the accumulation in cells of 12-hydroxyjasmonic acid (12-HOJA), 12-hydroxyjasmonoyl-L-isoleucine (12-HOJA-Ile) and 12-carboxyjasmonoyl-L-isoleucine (12-HOOCJA-Ile) and 12-O-glucosyl-jasmonic acid (12-O-Glc-JA), as well as 9,10-dihydrojasmonic acid (DHJA) in growth medium. Show less
Brouwers, H.; Hegedus, J. von; Toes, R.; Kloppenburg, M.; Ioan-Facsinay, A. 2015
In today__s world, more people die from complications of overweight than from underweight. But not all individuals are equally prone to develop metabolic complications, such as obesity and insulin... Show moreIn today__s world, more people die from complications of overweight than from underweight. But not all individuals are equally prone to develop metabolic complications, such as obesity and insulin resistance. This thesis focuses on the differences in the energy and fatty acid metabolism that play a role in the susceptibility for metabolic complications. We have investigated certain existing associations between genetic clues and a disturbed energy metabolism, in order to construct a more refined mechanism of action for this genetic association. This knowledge could be used to more precisely target the causal proteins and pathways involved in the development of obesity. We have also investigated the role of fatty acid metabolism in the fat tissue of obese humans and mice. In this way, we have found a direct link in both humans and mice between fatty acids and inflammation, which is relevant for metabolic diseases such as obesity and insulin resistance. Show less
