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Urinary Resveratrol Metabolites Output: Differential Associations with Cardiometabolic Markers and Liver Enzymes in House-Dwelling Subjects Featuring Metabolic Syndrome

1
Department of Nutrition, Food Science and Physiology, Center for Nutrition Research, University of Navarra, 31008 Pamplona, Spain
2
Consorcio CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), 28029 Madrid, Spain
3
Department of Nutritional Sciences, School of Life Course Sciences, Faculty of Life Sciences and Medicine, King’s College London, London SE1 9NH, UK
4
Department of Preventive Medicine and Public Health, University of Navarra, 31008 Pamplona, Spain
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Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Carlos III (ISCIII), 28029 Madrid, Spain
6
Institute of Biomedicine (IBIOMED), University of León, 24071 León, Spain
7
Department of Internal Medicine, IDIBAPS, Hospital Clinic, University of Barcelona, 08036 Barcelona, Spain
8
Department of Nutrition, Food Sciences and Gastronomy, XaRTA, INSA-UB, School of Pharmacy and Food Sciences, Nutrition and Food Safety Research Institute, University of Barcelona, 08028 Barcelona, Spain
9
Cardiovascular Risk and Nutrition Research Group (CARIN), Hospital del Mar Research Institute (IMIM), 08007 Barcelona, Spain
10
CIBER Fragilidad y Envejecimiento Saludable (CIBERFES), Institute of Health Carlos III, 28029 Madrid, Spain
11
Institute of Nutrition and Food Safety (INSA-UB), University of Barcelona, Santa Coloma de Gramenet, 08921 Barcelona, Spain
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Departament de Bioquímica i Biotecnologia, Universitat Rovira i Virgili, Unitat de Nutrició Humana, 43201 Reus, Spain
13
Institut d’Investigació Pere Virgili (IISPV), Hospital Universitari Sant Joan de Reus, 43204 Reus, Spain
14
Department of Endocrinology, Instituto de Investigación Biomédica de Málaga-IBIMA, University of Málaga, Virgen de la Victoria Hospital, 29010 Málaga, Spain
15
Research Group on Community Nutrition & Oxidative Stress, University of Balearic Islands, 07122 Palma de Mallorca, Spain
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Research Group on Nutritional Epidemiology & Cardiovascular Physiopathology (NUTRECOR), Health Research Institute of the Balearic Islands (IdISBa), University Hospital Son Espases (HUSE), 07120 Palma de Mallorca, Spain
17
Lipids and Vascular Risk Unit, Internal Medicine, Hospital Universitario de Bellvitge, Hospitalet de Llobregat, 08908 Barcelona, Spain
18
Precision Nutrition Program, IMDEA Food, CEI UAM + CSIC, 28049 Madrid, Spain
*
Author to whom correspondence should be addressed.
On behalf of PREDIMED-Plus Investigators.
Molecules 2020, 25(18), 4340; https://doi.org/10.3390/molecules25184340
Received: 31 July 2020 / Revised: 16 September 2020 / Accepted: 18 September 2020 / Published: 22 September 2020
(This article belongs to the Section Natural Products Chemistry)
Metabolic syndrome (MetS) components are strongly associated with increased risk of non-alcoholic fatty liver disease (NAFLD) development. Several studies have supported that resveratrol is associated with anti-inflammatory and antioxidant effects on health status. The main objective of this study was to assess the putative associations between some urinary resveratrol phase II metabolites, cardiometabolic, and liver markers in individuals diagnosed with MetS. In this cross-sectional study, 266 participants from PREDIMED Plus study (PREvención con DIeta MEDiterránea) were divided into tertiles of total urinary resveratrol phase II metabolites (sum of five resveratrol conjugation metabolites). Urinary resveratrol metabolites were analyzed by ultra- performance liquid chromatography coupled to triple quadrupole mass spectrometry (UPLC-Q-q-Q MS), followed by micro-solid phase extraction (µ-SPE) method. Liver function markers were assessed using serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyl transferase (GGT). Moreover, lipid profile was measured by triglycerides, very-low-density lipoprotein cholesterol (VLDL-c), and total cholesterol/high-density lipoprotein ratio (total cholesterol/HDL). Linear regression adjusted models showed that participants with higher total urine resveratrol concentrations exhibited improved lipid and liver markers compared to the lowest tertile. For lipid determinations: log triglycerides (βT3= −0.15, 95% CI; −0.28, −0.02, p-trend = 0.030), VLDL-c, (βT3= −4.21, 95% CI; −7.97, −0.46, p-trend = 0.039), total cholesterol/HDL ratio Moreover, (βT3= −0.35, 95% CI; −0.66, −0.03, p-trend = 0.241). For liver enzymes: log AST (βT3= −0.12, 95% CI; −0.22, −0.02, p-trend = 0.011, and log GGT (βT3= −0.24, 95% CI; −0.42, −0.06, p-trend = 0.002). However, there is no difference found on glucose variables between groups. To investigate the risk of elevated serum liver markers, flexible regression models indicated that total urine resveratrol metabolites were associated with a lower risk of higher ALT (169.2 to 1314.3 nmol/g creatinine), AST (599.9 to 893.8 nmol/g creatinine), and GGT levels (169.2 to 893.8 nmol/g creatinine). These results suggested that higher urinary concentrations of some resveratrol metabolites might be associated with better lipid profile and hepatic serum enzymes. Moreover, urinary resveratrol excreted showed a reduced odds ratio for higher liver enzymes, which are linked to NAFLD. View Full-Text
Keywords: antioxidant; inflammation; liver enzymes; metabolic syndrome; non-alcoholic fatty liver disease; resveratrol antioxidant; inflammation; liver enzymes; metabolic syndrome; non-alcoholic fatty liver disease; resveratrol
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MDPI and ACS Style

Bullón-Vela, V.; Abete, I.; Zulet, M.A.; Xu, Y.; Martínez-González, M.A.; Sayón-Orea, C.; Ruiz-Canela, M.; Toledo, E.; Sánchez, V.M.; Estruch, R.; Lamuela-Raventós, R.M.; Almanza-Aguilera, E.; Fitó, M.; Salas-Salvadó, J.; Díaz-López, A.; Tinahones, F.J.; Tur, J.A.; Romaguera, D.; Konieczna, J.; Pintó, X.; Daimiel, L.; Rodriguez-Mateos, A.; Alfredo Martínez, J. Urinary Resveratrol Metabolites Output: Differential Associations with Cardiometabolic Markers and Liver Enzymes in House-Dwelling Subjects Featuring Metabolic Syndrome. Molecules 2020, 25, 4340. https://doi.org/10.3390/molecules25184340

AMA Style

Bullón-Vela V, Abete I, Zulet MA, Xu Y, Martínez-González MA, Sayón-Orea C, Ruiz-Canela M, Toledo E, Sánchez VM, Estruch R, Lamuela-Raventós RM, Almanza-Aguilera E, Fitó M, Salas-Salvadó J, Díaz-López A, Tinahones FJ, Tur JA, Romaguera D, Konieczna J, Pintó X, Daimiel L, Rodriguez-Mateos A, Alfredo Martínez J. Urinary Resveratrol Metabolites Output: Differential Associations with Cardiometabolic Markers and Liver Enzymes in House-Dwelling Subjects Featuring Metabolic Syndrome. Molecules. 2020; 25(18):4340. https://doi.org/10.3390/molecules25184340

Chicago/Turabian Style

Bullón-Vela, Vanessa; Abete, Itziar; Zulet, Maria A.; Xu, Yifan; Martínez-González, Miguel A.; Sayón-Orea, Carmen; Ruiz-Canela, Miguel; Toledo, Estefanía; Sánchez, Vicente M.; Estruch, Ramon; Lamuela-Raventós, Rosa M.; Almanza-Aguilera, Enrique; Fitó, Montserrat; Salas-Salvadó, Jordi; Díaz-López, Andrés; Tinahones, Francisco J.; Tur, Josep A.; Romaguera, Dora; Konieczna, Jadwiga; Pintó, Xavier; Daimiel, Lidia; Rodriguez-Mateos, Ana; Alfredo Martínez, José. 2020. "Urinary Resveratrol Metabolites Output: Differential Associations with Cardiometabolic Markers and Liver Enzymes in House-Dwelling Subjects Featuring Metabolic Syndrome" Molecules 25, no. 18: 4340. https://doi.org/10.3390/molecules25184340

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