Postprandial triglyceride-rich lipoproteins promote lipid accumulation and apolipoprotein B-48 receptor transcriptional activity in human circulating and murine bone marrow neutrophils in a fatty acid-dependent manner

5 Figuras.-- 1 TablaScope: Postprandial triglyceride-rich lipoproteins (TRLs) promote atherosclerosis. Recent research points the bone marrow (BM) as a primary site in atherosclerosis. We elucidated how the acute administration of MUFAs, omega-3 PUFAs and saturated fatty acids (SFAs) affects human circulating and murine BM neutrophil lipid accumulation and functionality. Methods and results: Postprandial hypertriglyceridemia was induced in healthy subjects and Apoe¿/¿ mice by the acute administration of dietary fats enriched in MUFAs, PUFAs or SFAs. Postprandial hypertriglyceridemia increased apolipoprotein-B48 receptor (ApoB48R) transcriptional activity that was linearly correlated with intracellular TGs accumulation in human circulating and murine BM neutrophils. MUFA and omega-3 PUFAs attenuated ApoB48R gene expression and intracellular TG accumulation compared to SFAs. TRLs induced apoB48R-dependent TG accumulation in human neutrophils ex-vivo. Murine BM neutrophils showed a decrease in surface L-selectin and an increase in TNF-¿ and IL-1ß mRNA expressions only after SFAs administration. TRLs enriched in SFAs induced BM neutrophil degranulation ex-vivo suggesting cell priming/activation. Conclusion: Postprandial TRLs disrupts the normal biology and function of circulating and BM neutrophils. MUFA- and omega-3 PUFA-rich dietary fats such as virgin olive oil or fish oil has the potential to prevent excessive neutrophil lipid accumulation and activation by targeting the fatty acid composition of TRLs.The work described herein was supported by the Ministerio de Economía y Competitividad Grant Numbers AGL2008‐02811 and AGL2016‐80852‐R. We wish to acknowledge Arturo Navarro at the Clinic Experimental Research Unit for Vascular Risk (UCAMI‐UCERV) at the University Hospital Virgen del Rocio for excellent technical assistance with human experiments