Volume 65, Issue 3, Pages (March 2004)

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Volume 65, Issue 3, Pages 1064-1075 (March 2004) A broad-based metabolic approach to study VLDL apoB100 metabolism in patients with ESRD and patients treated with peritoneal dialysis Berthil H.C.M.T. Prinsen, Ton J. Rabelink, Johannes A. Romijn, Peter H. Bisschop, Martina M.J. de Barse, José de Boer, Timon W. van Haeften, P. Hugh R. Barrett, Ruud Berger, Monique G.M. de Sain-van der Velden Kidney International Volume 65, Issue 3, Pages 1064-1075 (March 2004) DOI: 10.1111/j.1523-1755.2004.00466.x Copyright © 2004 International Society of Nephrology Terms and Conditions

Figure 1 Hypothetical model for hypertriglyceridemia in end-stage renal disease (ESRD). One of the key players is insulin. Reduced insulin sensitivity present in peripheral tissues in ESRD (1), contributes to increased free fatty acid (FFA) release (2). These free fatty acids are subsequently oxidized or esterified, where after, if not stored, free fatty acids are directed to very low-density lipoprotein (VLDL) apolipoprotein B (apoB100) synthesis (3). As peritoneal dialysis treatment is initiated, aggravation of hypertriglyceridemia occurs, that could be the result of stimulation of de novo lipogenesis (DNL) due to glucose loading (4) or substantial protein loss (5). High plasma concentrations of triglyceride (TG)-rich lipoproteins leads to increased release of free fatty acids and generation of remnants as a result of lipolysis by lipoprotein lipase (LPL). These free fatty acids are subjected to the liver, thereby setting up a vicious cycle and further driving VLDL production. Kidney International 2004 65, 1064-1075DOI: (10.1111/j.1523-1755.2004.00466.x) Copyright © 2004 International Society of Nephrology Terms and Conditions

Figure 2 Infusion scheme. (A) Day 1. Subjects received a priming dose of [1-13C]-valine directly followed by a continuous infusion of the same amount of tracer for 600 minutes. In addition, subjects received every half hour 500mg [1-13C]-acetate, which was administered orally. The arrows indicate the time-points for collection of blood. (B) Day 2. Subjects received a continuous infusion of [2,2-2H2]-palmitate 70 minutes before starting the clamp and during the last 70 minutes of the clamp. Euglycemic hyperinsulinemic clamp was performed at an insulin infusion rate of 1.2 U/m2/hour. The arrows indicate the time-points for collection of blood for determining of free fatty acid release. Additionally blood samples were taken in order to measure insulin sensitivity. Kidney International 2004 65, 1064-1075DOI: (10.1111/j.1523-1755.2004.00466.x) Copyright © 2004 International Society of Nephrology Terms and Conditions

Figure 3 Multicompartmental model for apolipoprotein B (apoB100) metabolism. Compartment 1 represents plasma valine into which the valine tracer was injected. Compartment 2 represents a delay compartment and valine in incorporated in very low-density lipoprotein (VLDL-1) apoB100, VLDL-2 apoB100, intermediate-density lipoprotein (IDL) apoB100, and low-density lipoprotein (LDL) apoB100 via compartments 3, 4, 5, and 6. The k-values represent rate constants. Kidney International 2004 65, 1064-1075DOI: (10.1111/j.1523-1755.2004.00466.x) Copyright © 2004 International Society of Nephrology Terms and Conditions