1. Overfeeding Saturated Fat Increases LDL (Low-Density Lipoprotein) Aggregation Susceptibility While Overfeeding Unsaturated Fat Decreases Proteoglycan-Binding of Lipoproteins
- Author
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Mari Lahelma, Martina B. Lorey, Leanne Hodson, Katariina Öörni, Panu K. Luukkonen, Hannele Yki-Järvinen, Sami Qadri, Petri T. Kovanen, Sanja Sädevirta, Tuulia Hyötyläinen, Maija Ruuth, Medicum, Research Programs Unit, University of Helsinki, HUS Internal Medicine and Rehabilitation, Department of Medicine, Clinicum, Doctoral Programme in Clinical Research, Molecular and Integrative Biosciences Research Programme, and Biosciences
- Subjects
proteoglykaanit ,Male ,intervention study ,Saturated fat ,030204 cardiovascular system & hematology ,chemistry.chemical_compound ,0302 clinical medicine ,Tandem Mass Spectrometry ,2. Zero hunger ,0303 health sciences ,rasvat ,sfingomyeliini ,aggregation ,aggregaatio ,ruokavalio ,LDL - Low density lipoprotein ,interventiotutkimus ,Middle Aged ,metabolomics ,3. Good health ,Lipoproteins, LDL ,nutrition ,Low-density lipoprotein ,ComputingMethodologies_DOCUMENTANDTEXTPROCESSING ,Female ,Proteoglycans ,lipids (amino acids, peptides, and proteins) ,3143 Nutrition ,Cardiology and Cardiovascular Medicine ,Sphingomyelin ,Protein Binding ,Adult ,ateroskleroosi ,Spectrometry, Mass, Electrospray Ionization ,medicine.medical_specialty ,lipoproteiinit ,Diet, High-Fat ,Independent predictor ,LDL ,sphingomyelin ,ravinto ,Protein Aggregates ,03 medical and health sciences ,Internal medicine ,medicine ,Humans ,metabolomiikka ,Nuclear Magnetic Resonance, Biomolecular ,030304 developmental biology ,Proteoglycan binding ,Unsaturated fat ,dietary fats ,Fats, Unsaturated ,lipoproteins ,Endocrinology ,low-density lipoprotein ,chemistry ,3121 General medicine, internal medicine and other clinical medicine ,atherosclerosis ,diet ,Clinical and Population Studies ,Chromatography, Liquid ,Lipoprotein - Abstract
Supplemental Digital Content is available in the text., Objective: We recently showed that measurement of the susceptibility of LDL (low-density lipoprotein) to aggregation is an independent predictor of cardiovascular events. We now wished to compare effects of overfeeding different dietary macronutrients on LDL aggregation, proteoglycan-binding of plasma lipoproteins, and on the concentration of oxidized LDL in plasma, 3 in vitro parameters consistent with increased atherogenicity. Approach and Results: The participants (36 subjects; age, 48±10 years; body mass index, 30.9±6.2 kg/m2) were randomized to consume an extra 1000 kcal/day of either unsaturated fat, saturated fat, or simple sugars (CARB) for 3 weeks. We measured plasma proatherogenic properties (susceptibility of LDL to aggregation, proteoglycan-binding, oxidized LDL) and concentrations and composition of plasma lipoproteins using nuclear magnetic resonance spectroscopy, and in LDL using liquid chromatography mass spectrometry, before and after the overfeeding diets. LDL aggregation increased in the saturated fat but not the other groups. This change was associated with increased sphingolipid and saturated triacylglycerols in LDL and in plasma and reduction of clusterin on LDL particles. Proteoglycan binding of plasma lipoproteins decreased in the unsaturated fat group relative to the baseline diet. Lipoprotein properties remained unchanged in the CARB group. Conclusions: The type of fat during 3 weeks of overfeeding is an important determinant of the characteristics and functional properties of plasma lipoproteins in humans. Registration: URL: http://www.clinicaltrials.gov; Unique identifier NCT02133144.
- Published
- 2021
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