Overfeeding Saturated Fat Increases LDL (Low-Density Lipoprotein) Aggregation Susceptibility While Overfeeding Unsaturated Fat Decreases Proteoglycan-Binding of Lipoproteins

Abstract

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/m 2 ) 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.

Pharmacometabolomic profiles in type 2 diabetic subjects treated with liraglutide or glimepiride

“…However, a recent study showed that overfeeding of carbohydrates increases levels of TG-SFAs, and decreases TG-PUFAs in LDL lipids, with no change in TG-MUFAs. Also, a high fat diet was found to have a similar, but stronger impact [ 48 ]. Since glimepiride administration did result in decreased TGs overall, and the difference between liraglutide and glimepiride treatments was mainly in TG-MUFA, it is unlikely that dietary factors had a major impact on the observed metabolic changes between the two treatments.…”

Lipidomics in nutrition research

“…In agreement with these overfeeding studies [38,39,43], a study of 2860 Chinese Singaporeans showed that higher saturated fat intake was associated with higher concentrations of specific sphingolipids, including ceramides, monohexosylceramides, dihexosylceramides, SMs, and sphingosine-1-phosphates [45]. Higher intake of PUFAs or proteins was shown to have an opposite effect.…”

“…To elucidate how the overfeeding impacts the metabolic health, a study conducted in Finland explored differences in plasma lipidome and lipoprotein profile of individuals subjected to overfeeding for 3 weeks (addition of 1000 kcal/day) with either unsaturated fat, saturated fat or simple sugars [38,39]. In contrast to unsaturated fat, overfeeding with saturated fat led to increase in intrahepatic triacylglycerols and increase in plasma ceramide levels [38].…”

Role of circulating sphingolipids in lipid metabolism: Why dietary lipids matter

“…In this regard, a pilot study in 6 hypertriglyceridemic men showed that the supplementation for 8 weeks with 3 g/d fish oil rich in EPA and DHA decreased fasting TG in plasma and large VLDL but also Cer concentrations in VLDL, without any modification of SM concentrations in VLDL ( 35 ). Regarding LDL, a dietary intervention study comparing the effects of different types of fats on plasma lipoproteins in 36 overweight middle-aged subjects showed that a 3-week consumption of extra daily 1,000 kCal coming from SFA resulted in modifications of LDL composition, independently of LDL cholesterol ( 36 ). Excess consumption of SFA (30 g coconut oil, 40 g butter, 100 g blue cheese 40% fat), but not unsaturated fats (36 g olive oil, 266 g pesto, 54 g pecan nuts, 20 g butter), increased concentrations of SM, Cer and saturated TG in LDL and increased their susceptibility to aggregate and consequently their atherogenicity.…”