# Lipoprotein(a) Lipidome: Responses to Reduced Dietary Saturated Fat Intake in Two Randomized Controlled Feeding Trials

## TL;DR

Reducing saturated fat intake increases Lp(a) levels and changes its lipid composition, suggesting diet affects cardiovascular risk factors.

## Contribution

The study reveals diet-induced changes in Lp(a) lipid composition, showing dynamic responses to dietary interventions.

## Key findings

- Replacing saturated fat with carbohydrates decreased ALDOPC in metabolically challenged individuals.
- Triacylglycerol species with more carbon atoms and double bonds increased with saturated fat reduction.
- Lp(a) lipid composition changes dynamically in response to dietary interventions.

## Abstract

Background/Objectives: An elevated level of lipoprotein(a) [Lp(a)] is a genetically determined risk factor for cardiovascular disease. The atherogenic properties of Lp(a) include attribution to its role as a carrier of oxidized phospholipids (OxPL). Despite genetic control, Lp(a) levels increase with dietary saturated fat (SFA) reduction. However, little is known about the impact of dietary factors on Lp(a) risk properties. Methods: We assessed total Lp(a)-OxPL concentration, Lp(a)-OxPL subspecies abundance, and Lp(a) lipidomics in response to SFA reduction in two multicenter, randomized, controlled, crossover feeding trials, DELTA (Dietary Effects on Lipoproteins and Thrombogenic Activity) 1 (96 healthy individuals) and 2 (79 metabolically challenged individuals). In both trials, significant increases in Lp(a) levels were reported previously. Results: While no between-diet differences in the concentrations of total Lp(a)-OxPL and four major OxPL subspecies (ALDOPC, POVPC, PAzPC, and PGPC) were observed in DELTA 1, ALDOPC decreased significantly in DELTA 2 when SFA was replaced with carbohydrates (p = 0.014). Of 440 individual lipid species annotated in an untargeted analysis of the Lp(a) lipidome, 87 lipids differed significantly (p < 0.05 adjusted for multiplicity) between diets, with triacylglycerol species showing the most pronounced changes in both trials. For all intervention diets, triacylglycerol species with a higher average number of carbon atoms and double bonds increased the most in abundance with SFA reduction. Conclusions: In parallel with an increase in plasma Lp(a) levels, significant changes in Lp(a) lipid composition occurred. The findings demonstrate the dynamic nature of intraindividual Lp(a) lipid composition in response to diet interventions.