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1 From the Department of Medicine, University of California, Davis.
2 Reprints not available. Address correspondence to L Berglund, Department of Medicine, University of California, Davis, UCD Medical Center, 4150 V Street, Suite G400, Sacramento, CA 95817. E-mail: lberglund{at}ucdavis.edu.
See corresponding article on page311.
Measurements of lipids and lipoproteins in the fasting state have contributed to our understanding of lipoprotein metabolism, and these measurements remain an important foundation for hypolipidemic interventions. However, humans spend a considerable amount of time in a postprandial state. Recently there has been a resurgent interest in understanding postprandial lipoprotein metabolism. This interest reflects early predictions that the postprandial state may affect atherogenesis (1), and in several recent studies, impaired postprandial triacylglycerol metabolism has indeed been associated with coronary artery disease (2–4). However, the postprandial response is complex, and both lipoprotein concentrations and composition are affected (5). To understand the impact of postprandial lipemia on atherogenesis, studies have been undertaken to ascertain 1) predictors of the postprandial response in different patient groups, 2) the effect of the postprandial state on the vascular wall and inflammatory factors, 3) the origin of circulating postprandial lipoprotein particles, and 4) the effect of hypolipidemic therapy on postprandial response in various patient groups (5–7). Most commonly, the incremental triacylglycerol response (ie, the incremental area under the postprandial triacylglycerol curve) has been used to assess postprandial response after an energy challenge. Both the magnitude and duration of the triacylglycerol response can be affected by diet, and these variables are both captured by using the incremental area under the postprandial triacylglycerol curve. Other variables, such as retinyl palmitate, remnant cholesterol concentrations, and the ratio of intestinally derived to hepatically derived apolipoprotein B (apo B) concentrations also have been measured (5). An early observation that has stood the test of time was that the baseline (or fasting) triacylglycerol concentration is a major predictor of the degree of change in postprandial triacylglycerol concentrations (8). This clearly indicates the need to take fasting triacylglycerol concentrations into account when assessing postprandial lipemia.
The advent of novel and more powerful methods, such as measurement of lipoprotein-specific apolipoprotein and lipid concentrations and analysis of genetic variants, allows a fuller understanding of the complexity of lipoprotein metabolism. An example of a recurring theme in this area is the issue of the contribution to the postprandial response of hepatically derived triacylglycerol-rich lipoproteins (containing apo B-100) compared with that of intestinally derived triacylglycerol-rich lipoproteins (containing apo B-48). These 2 lipoprotein fractions compete in the postprandial state for the same clearing mechanism, and consequently their metabolism is linked (9). Under fasting conditions, apo B-48 constitutes only a minor part of the total apo B associated with triacylglycerol-rich lipoproteins, and even during postprandial conditions, the relative contribution of apo B-48 is modest (5). However, because apo B-48–containing chylomicrons are larger than apo B-100–containing VLDLs, the amount of triacylglycerol carried by apo B-48–containing particles can be substantial. Whether the balance between intestinally derived and hepatically derived lipoproteins can be modulated by different disease states has not been fully explored.
In the present issue of the Journal, Couillard et al (10) focus on the relative contribution of these 2 apolipoproteins to the postprandial response in obese individuals. The authors analyzed dietary fat tolerance in 50 men between the ages of 28 and 67 y with varying degrees of obesity. As expected, hepatically derived, apo B-100–containing lipoproteins contributed to most of the postprandial increase in the number of triacylglycerol-rich particles, and the apo B-48 response to the fat load was the best predictor of the increase in triacylglycerol in the chylomicron-VLDL fraction. The fasting triacylglycerol concentration was the best predictor of the postprandial response of both apo B-48 and apo B-100 concentrations. The authors also characterized the postprandial response of the triacylglycerol-rich lipoprotein subpopulation, dividing the particle spectrum into large, medium, and small particles. In approximately one-quarter of the subjects, the number of small particles decreased postprandially, and this was accompanied by an increase in the total triacylglycerol–apo B ratio in the triacylglycerol-rich lipoprotein fraction. As pointed out by the authors, a likely explanation for this pattern is a relative decrease in lipoprotein lipase activity, resulting in a sluggish conversion of the larger triacylglycerol-rich lipoproteins to smaller particles through lipolysis. Interestingly, the subjects characterized by this postprandial pattern had several features of the insulin resistance syndrome, including high fasting triacylglycerol and insulin concentrations, high visceral fat deposition, and a high ratio of total to HDL cholesterol. It is well known that this state is also characterized by an increase of smaller, denser HDL and LDL particles, and the authors conclude that such a pattern postprandially may be associated with an increased cardiovascular risk.
The results of this study may increase our attention to the possible implications of a deranged postprandial lipoprotein metabolism. The study also underscores that similar mechanisms modulate the postprandial response in nonobese and obese subjects. Thus, the fasting triacylglycerol concentration was a major predictor of the postprandial response, and a relative lipoprotein lipase deficiency may result in a slower conversion of larger triacylglycerol-rich lipoproteins to smaller particles. Postprandial metabolism may not necessarily have any unique qualitative features in obesity—the findings most likely represent the consequences of an increased metabolic stress in which the challenge of obesity may uncover limitations of the clearing system. The present findings regarding the lipoprotein subfraction distribution point to the importance of a more comprehensive understanding of postprandial lipoprotein metabolism. Because impaired postprandial metabolism may increase the atherogenic potential, future studies focused on the underlying mechanisms are warranted.
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