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

Cardiovascular Diabetology

Antonio Segura-Carretero¹  Concepción M. Aguilera²  Angel Gil²  Catalina Núñez-Roa³  Sonia Fernández-Veledo³  Victoria Ceperuelo-Mallafré⁴  Joan Vendrell⁴  Isabelle Kohler⁵  Patrick C. N. Rensen⁶  Xinyu Di⁷  José V. García-Lario⁸  Jose M. Llamas-Elvira⁹  Lucas Jurado-Fasoli^1,10  Jonatan R. Ruiz^1,10  Francisco J. Osuna-Prieto^1,11  Huiwen Xu^1,12  Lourdes Ortiz-Alvarez^1,12  Borja Martinez-Tellez^1,13 

[1] Department of Analytical Chemistry, University of Granada, Granada, Spain;Research and Development of Functional Food Center (CIDAF), Granada, Spain;Department of Biochemistry and Molecular Biology II, “José Mataix Verdú” Institute of Nutrition and Food Technology (INYTA), Biomedical Research Center (CIBM), University of Granada, Granada, Spain;Biohealth Research Institute in Granada (Ibs, GRANADA), Granada, Spain;CIBER Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Madrid, Spain;Department of Endocrinology and Nutrition and Research Unit, University Hospital of Tarragona Joan XXIII-Institut d ́Investigació Sanitària Pere Virgili (IISPV), Tarragona, Spain;CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM)-Instituto de Salud Carlos III, Madrid, Spain;Department of Endocrinology and Nutrition and Research Unit, University Hospital of Tarragona Joan XXIII-Institut d ́Investigació Sanitària Pere Virgili (IISPV), Tarragona, Spain;CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM)-Instituto de Salud Carlos III, Madrid, Spain;Rovira i Virgili University, Tarragona, Spain;Division of BioAnalytical Chemistry, Vrije Universiteit Amsterdam, Amsterdam Institute of Molecular and Life Sciences (AIMMS), Amsterdam, The Netherlands;Center for Analytical Sciences Amsterdam, Amsterdam, The Netherlands;Division of Endocrinology and Einthoven Laboratory for Experimental Vascular Medicine, Department of Medicine, Leiden University Medical Center, Leiden, The Netherlands;Division of Systems Biomedicine and Pharmacology, Leiden Academic Center for Drug Research, Leiden University, Leiden, The Netherlands;Hospital Universitario Clínico San Cecilio, Granada, Spain;Nuclear Medicine Service, Virgen de las Nieves University Hospital, Biohealth Research Institute in Granada (Ibs. GRANADA), Granada, Spain;PROFITH (PROmoting FITness and Health Through Physical Activity) Research Group, Department of Physical Education and Sport, Faculty of Sport Sciences, University of Granada, Granada, Spain;PROFITH (PROmoting FITness and Health Through Physical Activity) Research Group, Department of Physical Education and Sport, Faculty of Sport Sciences, University of Granada, Granada, Spain;Department of Analytical Chemistry, University of Granada, Granada, Spain;Research and Development of Functional Food Center (CIDAF), Granada, Spain;PROFITH (PROmoting FITness and Health Through Physical Activity) Research Group, Department of Physical Education and Sport, Faculty of Sport Sciences, University of Granada, Granada, Spain;Department of Biochemistry and Molecular Biology II, “José Mataix Verdú” Institute of Nutrition and Food Technology (INYTA), Biomedical Research Center (CIBM), University of Granada, Granada, Spain;PROFITH (PROmoting FITness and Health Through Physical Activity) Research Group, Department of Physical Education and Sport, Faculty of Sport Sciences, University of Granada, Granada, Spain;Division of Endocrinology and Einthoven Laboratory for Experimental Vascular Medicine, Department of Medicine, Leiden University Medical Center, Leiden, The Netherlands;

关键词: Obesity;    Visceral adiposity;    Inflammation;    Oxylipins;    Succinate;   

DOI  :  10.1186/s12933-021-01333-3

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY