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

F.J. Osuna-Prieto, B. Martinez-Tellez, L. Ortiz-Alvarez, X. Di, L. Jurado-Fasoli, H. Xu, V. Ceperuelo-Mallafré, C. Núñez-Roa, I. Kohler, A. Segura-Carretero, J.V. García-Lario, A. Gil, C.M. Aguilera, J.M. Llamas-Elvira, P.C.N. Rensen, J. Vendrell, J.R. Ruiz, S. Fernández-Veledo

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

© 2021, The Author(s).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 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 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. Results: Individuals 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. Conclusions: Plasma 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.
Original languageEnglish
Article number151
JournalCardiovascular Diabetology
Volume20
Issue number1
DOIs
Publication statusPublished - 1 Dec 2021

Funding

The study was supported by the Spanish Ministry of Economy and Competitiveness via Retos de la Sociedad (DEP2016-79512-R to JRR and RTI2018-093919-B to SFV), and by European Regional Development Funds (ERDF), the Spanish Ministry of Education (FPU16/02828, FPU16/05159, FPU17/01523 and FPU19/01609), the University of Granada Plan Propio de Investigación 2016-Excellence actions–Unit of Excellence on Exercise and Health (UCEES), and the Junta de Andalucía, Consejería de Conocimiento, Investigación y Universidades (ERDF: ref. SOMM17/6107/UGR). The Spanish Ministry of Science and Innovation (PI20/00095 to VCM and PI20/00338 to JV) co-financed by the European Regional Development Fund (ERDF). VCM acknowledges support from the Ramón y Cajal program (RYC2019-026490-I) from the Spanish Ministry of Science and Innovation, co-financed by the ERDF. The study was also supported by Fundación Bancaria Caixa d’Estalvis i Pensions de Barcelona (HR20-00051 to S.F.-V.), The Netherlands CardioVascular Research Initiative: ‘the Dutch Heart Foundation, Dutch Federation of University Medical Centers, The Netherlands Organization for Health Research and Development and the Royal Netherlands Academy of Sciences’ (CVON2017-20 GENIUS-2) to PCNR, and the Chinese Scholarship Council (CSC, No. 201707060012) to XD. SFV acknowledges support from the Miguel Servet tenure-track program (CP10/00438 and CPII16/00008) from the Fondo de Investigación Sanitaria, co-financed by the ERDF. BMT is supported by the individual postdoctoral grant from the Fundación Alfonso Martin Escudero, 2020. This study is part of a Ph.D. thesis conducted in the Biomedicine Doctoral Studies of the University of Granada, Spain.

FundersFunder number
Dutch Federation of University Medical Centers
Fondo de Investigación Sanitaria
Miguel ServetCP10/00438, CPII16/00008
Royal Netherlands Academy of SciencesCVON2017-20 GENIUS-2
University of Granada Plan Propio de Investigación
Fundación Alfonso Martín Escudero
“la Caixa” FoundationHR20-00051
ZonMw
Hartstichting
Ministerio de Educación, Cultura y DeporteFPU16/05159, FPU16/02828, FPU17/01523, FPU19/01609
Ministerio de Economía y CompetitividadRTI2018-093919-B, DEP2016-79512-R
China Scholarship Council201707060012
Ministerio de Ciencia e InnovaciónPI20/00338, PI20/00095
European Regional Development FundRYC2019-026490-I
Consejería de Conocimiento, Investigación y Universidad, Junta de AndalucíaSOMM17/6107/UGR

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