Pre-meal protein intake alters postprandial plasma metabolome in subjects with metabolic syndrome
We examined the effect on the postprandial plasma metabolome of protein pre-meals before a fat-rich main meal.
Two randomized, cross-over meal studies were conducted to test the dose–response effect (0 g, 10 g, 20 g) of a pre-meal with whey protein (WP) (PREMEAL I), and the effect of protein quality (10 g WP, casein, or gluten) and timing (− 15 min vs − 30 min) of the pre-meal (PREMEAL II). Participants with metabolic syndrome received one of the test meals on each test day, − 15 min (or − 30 min) prior to a standardized fat-rich breakfast. Plasma samples were collected at − 15 min (or − 30 min), 0, 120, 240 a nd 360 min and analyzed using liquid chromatography–mass spectrometry with an untargeted method.
Pre-meal WP intake elevated plasma branched-chain amino acids (BCAA), aromatic amino acids and methionine and decreased plasma LPC (16:0) and PC (32:1) levels before the main meal. Early (− 15 to 0 min) aromatic amino acids and BCAA in response to pre-meal WP partially predict the glucose and insulin response after the main meal. A pre-meal with WP altered the postprandial plasma metabolic pattern of acyl-carnitines, specific PCs, LPCs and LPEs, betaine, citric acid, linoleic acid, and β-hydroxypalmitic acid compared to no pre-meal. The casein and WP pre-meals exhibited similar postprandial amino acid responses whereas a pre-meal with gluten resulted in lower levels of plasma amino acids and its metabolites.
A pre-meal with protein affects the postprandial metabolic pattern indicating facilitated glucose and lipid disposal from plasma in participants with metabolic syndrome.
KeywordsInsulin resistance Metabolites Second meal Effect biomarkers UPLC–ESI–Q-TOF–MS
Area under the curve
Collision dissociation energies
Free fatty acids
Homeostatic model assessment for insulin resistance
Liquid chromatography/mass spectrometry
Mass to charge ratio
Tandem mass spectrometry
Principal component analysis
Partial least squares discriminant analysis
Quadrupole-time of flight mass spectrometer
Area under the receiver-operator curve
Type 2 diabetes mellitus
Ultra-performance liquid chromatography
Variable importance in projection
AB and KH planned and conducted the intervention studies. CTP conducted the metabolomics workflow and data analysis and drafted the manuscript. GP and LOD contributed to data analysis, identification and interpretation. LOD, CTP, AB, GP, and KH reviewed the manuscript. All the authors have read and approved the final version.
This work was supported by grants from the Danish Dairy Research Foundation and the Innovation Fund—MERITS (4105-00002B). CTP was supported by a Ph.D. grant from the Department of Nutrition, Exercise and Sports, University of Copenhagen and Hacettepe University. AB was supported by research grants from The Danish Diabetes Academy supported by the Novo Nordisk Foundation, Aarhus University and The Research Foundation of the Department of Endocrinology and Internal Medicine, Aarhus University Hospital. Protein powder was kindly provided by Arla Foods Ingredients Group P/S.
Compliance with ethical standards
Conflict of interest
CTP, GP, KH and LOD declare no conflicts of interest. AB has after termination of the study been employed at Arla Foods Ingredients Group P/S.
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