Warmbrunn Moritz V, Koopen Annefleur M, de Clercq Nicolien C, de Groot Pieter F, Kootte Ruud S, Bouter Kristien E C, Ter Horst Kasper W, Hartstra Annick V, Serlie Mireille J, Ackermans Mariette T, Soeters Maarten R, van Raalte Daniel H, Davids Mark, Nieuwdorp Max, Groen Albert K
Department of Internal and Vascular Medicine, Amsterdam University Medical Centers, Location AMC, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
Department of Endocrinology and Metabolism, Amsterdam UMC, Location AMC at University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
Metabolites. 2021 Apr 13;11(4):236. doi: 10.3390/metabo11040236.
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 ( = 132) were analyzed together with clinical parameters. In a subset of MetSyn participants, CVD risk was calculated using the Framingham score ( = 111), and lipolysis ( = 39) was measured by a two-step hyperinsulinemic euglycemic clamp using [1,1,2,3,3-H5] 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.
代谢综合征（MetSyn）是2型糖尿病和心血管疾病（CVD）的重要危险因素。本研究旨在找出患有MetSyn的胰岛素抵抗和非胰岛素抵抗受试者之间不同的血浆代谢物谱，并评估MetSyn代谢物谱是否与CVD风险和脂质通量相关。在一项横断面研究中，对未接受过治疗的患有MetSyn的男性（n = 132）进行了非靶向代谢组学分析，并结合临床参数进行研究。在一部分MetSyn参与者中，使用弗明汉评分法计算CVD风险（n = 111），并通过两步高胰岛素正常血糖钳夹法，使用[1,1,2,3,3-H5]甘油测量脂肪分解（n = 39），以计算脂肪分解抑制率。外周胰岛素抵抗与脂肪酸代谢和甘油磷酸胆碱有关。有趣的是，尽管胰岛素抵抗被认为是CVD的一个危险因素，但我们观察到与胰岛素抵抗相关的代谢物和与CVD风险相关的代谢物之间几乎没有对应关系。后者主要属于雄激素类固醇、脂肪酸、磷脂酰乙醇胺和磷脂酰胆碱途径。这些数据为轻度MetSyn病理生理学中的代谢变化以及与脂质代谢相关的MetSyn CVD风险提供了新的见解。前瞻性研究可能会关注此处确定的生物标志物的病理生理作用。
