The chylomicron saga: time to focus on postprandial metabolism Alejandro Gugliucci Glycation, Oxidation and Disease Laboratory, Department of Research, Touro University California, Vallejo, CA, United States Over the past three decades, statins have had tremendous therapeutic success, making the field of atherosclerosis somewhat LDL-centric and dismissing the relevance of triglycerides (TG), particularly chylomicrons, in atherogenesis. However, 50% of patients on statins are at risk of developing atherosclerotic cardiovascular disease (ASCVD) and cannot achieve their target LDL-C levels. This residual risk is partly mediated by triglyceride-rich lipoproteins (TRL) and their remnants. Zilversmit proposed in 1979 that atherosclerosis is a postprandial event, suggesting that remnant cholesterol-rich chylomicron (CM) and very-low density lipoprotein (VLDL) particles play a role in atherogenesis. This narrative review addresses recent advances in understanding postprandial dyslipidemia, focusing on the primary metabolic pathways of chylomicrons, the critical role of lipoprotein lipase and apoCIII, the importance of these particles' fluxes in the postprandial period, their catabolic rate, the complexity of testing postprandial metabolism, and the role of angiopoietin-like proteins in the partition of CM during the fed cycle. It also discusses the dysregulation of postprandial lipid metabolism in insulin resistance states and consequent CVD risk, the clinical evaluation of postprandial dyslipidemia, current research limitations, and potential future study directions. Keywords: chylomicron, triglyceride-rich lipoproteins, lipoprotein lipase, ApoCIII, ANGPTL, MetS, postprandial, atherosclerosis Chylomicrons are large triglyceride-rich lipoproteins produced by enterocytes from dietary lipids, specifically cholesterol and fatty acids. They transport phospholipids and esterified cholesterol, similar to other lipoproteins. Chylomicrons are the largest lipoproteins, ranging from 75-1,200 nm in diameter. They have a density below 0.93 g/ml and the lowest protein composition of any lipoprotein at just 2%. Chylomicrons are produced by enterocytes through a complex process involving the re-esterification of fatty acids and 2-monoglycerides (2-MG) in the endoplasmic reticulum (ER). The main pathway for TG production in the small intestine is the MGAT pathway, which involves the microsomal enzyme MGAT, which catalyzes the acyl-CoA-dependent esterification of 2-MG to produceThe chylomicron saga: time to focus on postprandial metabolism Alejandro Gugliucci Glycation, Oxidation and Disease Laboratory, Department of Research, Touro University California, Vallejo, CA, United States Over the past three decades, statins have had tremendous therapeutic success, making the field of atherosclerosis somewhat LDL-centric and dismissing the relevance of triglycerides (TG), particularly chylomicrons, in atherogenesis. However, 50% of patients on statins are at risk of developing atherosclerotic cardiovascular disease (ASCVD) and cannot achieve their target LDL-C levels. This residual risk is partly mediated by triglyceride-rich lipoproteins (TRL) and their remnants. Zilversmit proposed in 1979 that atherosclerosis is a postprandial event, suggesting that remnant cholesterol-rich chylomicron (CM) and very-low density lipoprotein (VLDL) particles play a role in atherogenesis. This narrative review addresses recent advances in understanding postprandial dyslipidemia, focusing on the primary metabolic pathways of chylomicrons, the critical role of lipoprotein lipase and apoCIII, the importance of these particles' fluxes in the postprandial period, their catabolic rate, the complexity of testing postprandial metabolism, and the role of angiopoietin-like proteins in the partition of CM during the fed cycle. It also discusses the dysregulation of postprandial lipid metabolism in insulin resistance states and consequent CVD risk, the clinical evaluation of postprandial dyslipidemia, current research limitations, and potential future study directions. Keywords: chylomicron, triglyceride-rich lipoproteins, lipoprotein lipase, ApoCIII, ANGPTL, MetS, postprandial, atherosclerosis Chylomicrons are large triglyceride-rich lipoproteins produced by enterocytes from dietary lipids, specifically cholesterol and fatty acids. They transport phospholipids and esterified cholesterol, similar to other lipoproteins. Chylomicrons are the largest lipoproteins, ranging from 75-1,200 nm in diameter. They have a density below 0.93 g/ml and the lowest protein composition of any lipoprotein at just 2%. Chylomicrons are produced by enterocytes through a complex process involving the re-esterification of fatty acids and 2-monoglycerides (2-MG) in the endoplasmic reticulum (ER). The main pathway for TG production in the small intestine is the MGAT pathway, which involves the microsomal enzyme MGAT, which catalyzes the acyl-CoA-dependent esterification of 2-MG to produce