Elevated plasma succinate levels are linked to higher cardiovascular disease risk factors in young adults

Abstract

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 infammatory and metabolic disorders in middle-aged adults. The relationship between plasma succinate levels and cardiovascular disease (CVD) risk in young adults is unknown. Methods: Cross-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 ftness 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. Results: Individuals with higher succinate levels had higher levels of visceral adipose tissue (VAT) mass (+42.5%), tri‑ glycerides (+63.9%), C-reactive protein (+124.2%), diastolic blood pressure (+5.5%), and pro-infammatory 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. Conclusions: Plasma succinate levels are linked to a specifc pro-infammatory omega-6 signature pattern and higher VAT levels, and seem to refect the cardiovascular status of young adults.