Higher Plasma Levels of Endocannabinoids and Analogues Correlate With a Worse Cardiometabolic Profile in Young Adults

Author:

Di Xinyu1ORCID,Martinez-Tellez Borja2345ORCID,Krekels Elke H J6,Jurado-Fasoli Lucas37,Osuna-Prieto Francisco J37,Ortiz-Alvarez Lourdes378,Hankemeier Thomas1ORCID,Rensen Patrick C N2ORCID,Ruiz Jonatan R357,Kohler Isabelle910ORCID

Affiliation:

1. Metabolomics and Analytics Centre, Leiden Academic Centre for Drug Research (LACDR), Leiden University , 2333 CC Leiden , The Netherlands

2. Department of Medicine, Division of Endocrinology, and Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center , 2333 ZA Leiden , The Netherlands

3. PROmoting FITness and Health through Physical Activity Research Group (PROFITH), Sport and Health University Research Institute (iMUDS), Department of Physical Education and Sports, Faculty of Sport Sciences, University of Granada , 18071 Granada , Spain

4. SPORT Research Group, CERNEP Research Center, University of Almería , 04120 Almería , Spain

5. CIBER de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III , 18100 Granada , Spain

6. Division of Systems Pharmacology and Pharmacy, Leiden Academic Centre for Drug Research, Leiden University , 2333 CC Leiden , The Netherlands

7. Instituto de Investigación Biosanitaria, ibs.Granada , 18012 Granada , Spain

8. Department of Biochemistry and Molecular Biology II, School of Pharmacy, University of Granada , 18071 Granada , Spain

9. Division of BioAnalytical Chemistry, Amsterdam Institute of Molecular and Life Sciences (AIMMS), Vrije Universiteit Amsterdam , 1081 HZ Amsterdam , The Netherlands

10. Center for Analytical Sciences Amsterdam , 1081 HZ Amsterdam , The Netherlands

Abstract

Abstract Context The endocannabinoid system (ECS) is a signaling system composed of endocannabinoids (eCBs), their receptors, and the enzymes involved in their synthesis and metabolism. Alterations in the ECS are linked to the development of cardiometabolic diseases. Objective Here, we investigated the relationship between plasma levels of eCBs and their analogues with body composition and cardiometabolic risk factors. Methods The study included 133 young adults (age 22.1 ± 2.2 years, 67% women). Fasting plasma levels of eCBs and their analogues were measured using liquid chromatography-tandem mass spectrometry. Body composition, brown adipose tissue (BAT) volume, glucose uptake, and traditional cardiometabolic risk factors were measured. Results Plasma levels of eCBs and several eCB analogues were positively correlated with adiposity and traditional cardiometabolic risk factors (eg, serum insulin and triacylglyceride levels, all r ≥ 0.17 and P ≤ .045). Plasma levels of 2-arachidonoyl glycerol and N-pentadecenoylethanolamine were negatively correlated with BAT volume and glucose uptake (all r ≤ −0.17 and P ≤ .047). We observed that the plasma levels of eCBs and their analogues were higher in metabolically unhealthy overweight–obese participants than in metabolically healthy overweight–obese participants. Conclusion Our findings show that the plasma levels of eCBs and their analogues are related to higher levels of adiposity and worse cardiometabolic profile.

Funder

Spanish Ministry of Economy and Competitiveness via the Fondo de Investigación Sanitaria del Instituto de Salud Carlos III

Retos de la Sociedad

European Regional Development Fund

Spanish Ministry of Education

Fundación Iberoamericana de Nutrición

Redes Temáticas de Investigación Cooperativa RETIC

AstraZeneca HealthCare Foundation

University of Granada Plan Propio de Investigación 2016 -Excellence actions: Unit of Excellence on Exercise and Health

Junta de Andalucía, Consejería de Conocimiento, Investigación y Universidades

Fundación Alfonso Martin Escudero

Netherlands CardioVascular Research Initiative: the Dutch Heart Foundation

Dutch Federation of University Medical Centers

Netherlands Organization for Health Research and Development

Royal Netherlands Academy of Arts and Sciences

China Scholarship Council

Publisher

The Endocrine Society

Subject

Biochemistry (medical),Clinical Biochemistry,Endocrinology,Biochemistry,Endocrinology, Diabetes and Metabolism

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