Abstract
BackgroundSuccinate 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.
Highlights
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
We examined whether succinate levels correlate with traditional and novel cardiovascular disease (CVD) risk factors in a well-phenotyped cohort of young adults
Participants The present study was conducted within the framework of the ACTIvating Brown Adipose Tissue through Exercise (ACTIBATE) study [33], a randomized controlled trial designed to determine the effect of exercise on brown adipose tissue (BAT) activity (Clinical trials identifier: NCT02365129)
Summary
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. Considered as a respiratory substrate of the mitochondrial electron transport chain, succinate is known to have additional physiological roles. It acts as a signaling molecule in both intracellular and extracellular compartments by binding and activating its cognate receptor, succinate receptor 1 (SUCNR1), known as G-protein coupled receptor 91 [9]. No study has investigated whether circulating succinate levels are associated with CVD risk, or whether it can be a biomarker of CVD risk in young adults [3,4,5,6]
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