TY - JOUR
T1 - Metabolite profile of treatment-naive metabolic syndrome subjects in relation to cardiovascular disease risk
AU - Warmbrunn, Moritz V.
AU - Koopen, Annefleur M.
AU - de Clercq, Nicolien C.
AU - de Groot, Pieter F.
AU - Kootte, Ruud S.
AU - Bouter, Kristien E. C.
AU - ter Horst, Kasper W.
AU - Hartstra, Annick V.
AU - Serlie, Mireille J.
AU - Ackermans, Mariette T.
AU - Soeters, Maarten R.
AU - van Raalte, Daniel H.
AU - Davids, Mark
AU - Nieuwdorp, Max
AU - Groen, Albert K.
N1 - Funding Information: M.V.W. is supported by CVON In Control II (grant number 2018.27). M.N. is supported by a ZONMW VIDI grant 2013 (016.146.327). Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/4/1
Y1 - 2021/4/1
N2 - Metabolic syndrome (MetSyn) is an important risk factor for type 2 diabetes and cardiovascular diseases (CVD). This study aimed to find distinct plasma metabolite profiles between insulin-resistant and non-insulin resistant subjects with MetSyn and evaluate if MetSyn metabolite profiles are related to CVD risk and lipid fluxes. In a cross-sectional study, untargeted metabolomics of treatment-naive males with MetSyn (n = 132) were analyzed together with clinical parameters. In a subset of MetSyn participants, CVD risk was calculated using the Framingham score (n = 111), and lipolysis (n = 39) was measured by a two-step hyperinsulinemic euglycemic clamp using [1,1,2,3,3-2H5] glycerol to calculate lipolysis suppression rates. Peripheral insulin resistance was related to fatty acid metabolism and glycerolphosphorylcholine. Interestingly, although insulin resistance is considered to be a risk factor for CVD, we observed that there was little correspondence between metabolites associated with insulin resistance and metabolites associated with CVD risk. The latter mainly belonged to the androgenic steroid, fatty acid, phosphatidylethanolamine, and phophatidylcholine pathways. These data provide new insights into metabolic changes in mild MetSyn pathophysiology and MetSyn CVD risk related to lipid metabolism. Prospective studies may focus on the pathophysiological role of the here-identified biomarkers.
AB - Metabolic syndrome (MetSyn) is an important risk factor for type 2 diabetes and cardiovascular diseases (CVD). This study aimed to find distinct plasma metabolite profiles between insulin-resistant and non-insulin resistant subjects with MetSyn and evaluate if MetSyn metabolite profiles are related to CVD risk and lipid fluxes. In a cross-sectional study, untargeted metabolomics of treatment-naive males with MetSyn (n = 132) were analyzed together with clinical parameters. In a subset of MetSyn participants, CVD risk was calculated using the Framingham score (n = 111), and lipolysis (n = 39) was measured by a two-step hyperinsulinemic euglycemic clamp using [1,1,2,3,3-2H5] glycerol to calculate lipolysis suppression rates. Peripheral insulin resistance was related to fatty acid metabolism and glycerolphosphorylcholine. Interestingly, although insulin resistance is considered to be a risk factor for CVD, we observed that there was little correspondence between metabolites associated with insulin resistance and metabolites associated with CVD risk. The latter mainly belonged to the androgenic steroid, fatty acid, phosphatidylethanolamine, and phophatidylcholine pathways. These data provide new insights into metabolic changes in mild MetSyn pathophysiology and MetSyn CVD risk related to lipid metabolism. Prospective studies may focus on the pathophysiological role of the here-identified biomarkers.
KW - Cardiovascular disease
KW - Lipolysis
KW - Metabolic syndrome
KW - Metabolomics
KW - Phospholipids
UR - http://www.scopus.com/inward/record.url?scp=85104961358&partnerID=8YFLogxK
U2 - https://doi.org/10.3390/metabo11040236
DO - https://doi.org/10.3390/metabo11040236
M3 - Article
C2 - 33924347
SN - 2218-1989
VL - 11
JO - Metabolites
JF - Metabolites
IS - 4
M1 - 236
ER -