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

doi:10.1186/s12933-021-01333-3

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

AIMMS

Research output: Contribution to Journal › Article › Academic › peer-review

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 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 language	English
Article number	151
Pages (from-to)	1-10
Number of pages	10
Journal	Cardiovascular Diabetology
Volume	20
Early online date	27 Jul 2021
DOIs	https://doi.org/10.1186/s12933-021-01333-3
Publication status	Published - 2021

Bibliographical note

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.

Funders	Funder number
Dutch Federation of University Medical Centers
Fondo de Investigación Sanitaria
Miguel Servet	CP10/00438, CPII16/00008
Royal Netherlands Academy of Sciences	CVON2017-20 GENIUS-2
University of Granada Plan Propio de Investigación
Fundación Alfonso Martín Escudero
“la Caixa” Foundation	HR20-00051
ZonMw
Hartstichting
Ministerio de Educación, Cultura y Deporte	FPU16/05159, FPU16/02828, FPU17/01523, FPU19/01609
Ministerio de Economía y Competitividad	RTI2018-093919-B, DEP2016-79512-R
China Scholarship Council	201707060012
Ministerio de Ciencia e Innovación	PI20/00338, PI20/00095
European Regional Development Fund	RYC2019-026490-I
Consejería de Conocimiento, Investigación y Universidad, Junta de Andalucía	SOMM17/6107/UGR

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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10.1186/s12933-021-01333-3

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Osuna-Prieto, F. J., Martinez-Tellez, B., Ortiz-Alvarez, L., Di, X., Jurado-Fasoli, L., Xu, H., Ceperuelo-Mallafré, V., Núñez-Roa, C., Kohler, I., Segura-Carretero, A., García-Lario, J. V., Gil, A., Aguilera, C. M., Llamas-Elvira, J. M., Rensen, P. C. N., Vendrell, J., Ruiz, J. R., & Fernández-Veledo, S. (2021). Elevated plasma succinate levels are linked to higher cardiovascular disease risk factors in young adults. Cardiovascular Diabetology, 20, 1-10. Article 151. https://doi.org/10.1186/s12933-021-01333-3

@article{c614f68328014e7396d085940ee8799e,

title = "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 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.",

author = "F.J. Osuna-Prieto and B. Martinez-Tellez and L. Ortiz-Alvarez and X. Di and L. Jurado-Fasoli and H. Xu and V. Ceperuelo-Mallafr{\'e} and C. N{\'u}{\~n}ez-Roa and I. Kohler and A. Segura-Carretero and J.V. Garc{\'i}a-Lario and A. Gil and C.M. Aguilera and J.M. Llamas-Elvira and P.C.N. Rensen and J. Vendrell and J.R. Ruiz and S. Fern{\'a}ndez-Veledo",

note = "{\textcopyright} 2021, The Author(s).",

year = "2021",

doi = "10.1186/s12933-021-01333-3",

language = "English",

volume = "20",

pages = "1--10",

journal = "Cardiovascular Diabetology",

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publisher = "BioMed Central Ltd",

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Osuna-Prieto, FJ, Martinez-Tellez, B, Ortiz-Alvarez, L, Di, X, Jurado-Fasoli, L, Xu, H, Ceperuelo-Mallafré, V, Núñez-Roa, C, Kohler, I, Segura-Carretero, A, García-Lario, JV, Gil, A, Aguilera, CM, Llamas-Elvira, JM, Rensen, PCN, Vendrell, J, Ruiz, JR & Fernández-Veledo, S 2021, 'Elevated plasma succinate levels are linked to higher cardiovascular disease risk factors in young adults', Cardiovascular Diabetology, vol. 20, 151, pp. 1-10. https://doi.org/10.1186/s12933-021-01333-3

TY - JOUR

T1 - Elevated plasma succinate levels are linked to higher cardiovascular disease risk factors in young adults

AU - Osuna-Prieto, F.J.

AU - Martinez-Tellez, B.

AU - Ortiz-Alvarez, L.

AU - Di, X.

AU - Jurado-Fasoli, L.

AU - Xu, H.

AU - Ceperuelo-Mallafré, V.

AU - Núñez-Roa, C.

AU - Kohler, I.

AU - Segura-Carretero, A.

AU - García-Lario, J.V.

AU - Gil, A.

AU - Aguilera, C.M.

AU - Llamas-Elvira, J.M.

AU - Rensen, P.C.N.

AU - Vendrell, J.

AU - Ruiz, J.R.

AU - Fernández-Veledo, S.

PY - 2021

Y1 - 2021

N2 - 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.

AB - 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.

U2 - 10.1186/s12933-021-01333-3

DO - 10.1186/s12933-021-01333-3

M3 - Article

SN - 1475-2840

VL - 20

SP - 1

EP - 10

JO - Cardiovascular Diabetology

JF - Cardiovascular Diabetology

M1 - 151

ER -

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

Abstract

Bibliographical note

Funding

UN SDGs

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