P319 - LIPIDOMICS ANALYSIS REVEALS A DRAMATIC REWIRING OF LIPID CLASSES INDEPENDENT OF FATTY ACID COMPOSITION IN THE PLANT-BASED VERSUS RED MEAT DIETS: INSIGHTS FROM THE FOOD-1 RANDOMIZED CROSS-OVER TRIAL

Background: Lipids are essential components of biological systems, serving structural, energetic, and signaling roles. Their levels and composition are shaped by genetic and environmental factors, including diet, and are closely linked to the development and progression of cardiovascular disease (CVD). Lipidomics—the comprehensive profiling of lipid species—offers a promising avenue to understand how dietary patterns influence lipid metabolism and CVD risk. Previous studies, including our own, have shown that substituting red meat with plant-based meat can reduce CVD risk factors such as trimethylamine N-oxide (TMAO), low-density lipoprotein (LDL) cholesterol, and systemic inflammation. However, the impact of such dietary shifts on the circulating lipidome remains poorly characterized.

METHODS AND RESULTS: We analyzed plasma samples from the FOOD-1 randomized, single-center, cross-over trial, which compared the effects of a 6-day plant-based versus red meat diet, separated by a 7-day washout period. Untargeted lipidomics was used to assess plasma lipid profiles. Clinical data were collected, including lipid panels (total triglycerides, HDL, LDL), C-reactive protein (CRP), TMAO, creatinine, blood pressure, body mass index (BMI), NT-proBNP, smoking status, medical history, and medication use. A total of 664 lipid species across 31 lipid subclasses were identified. Compared to the red meat diet, 105 lipids were upregulated and 197 were downregulated following the plant-based diet. Glycerolipids, fatty acyls, oxidized lipids, and cholesterol esters were significantly downregulated while ether phosphatidylserines, lyso-N-acyl-phosphatidylethanolamines (LNAPE), and mono-methyl-phosphatidylethanolamines were upregulated in the plant-based meat diet in comparison to the red meat diet (Figures 1 and 2). Partial Least Squares Discriminant Analysis (PLS-DA) revealed a clear separation between diet groups (Figure 1A), driven by lipids involved in the phosphatidylethanolamine (PE) methylation pathway, N-acylethanolamines (NAE), and LNAPE (Figure 1B). Notably, phosphatidylcholines (PC) and PEs were significantly altered, with elevated circulating PCs in the plasma of red meat consumers. Notably, the shift in diet resulted in extensive remodeling of lipid classes, independent of fatty acid composition (Figure 2).

Conclusion: These findings reveal novel lipidomic signatures associated with plant-based meat consumption and highlight potential metabolic pathways that may mediate CVD risk reduction.