OBJECTIVE - The purpose of this study was to examine the effect of weight loss on LDL and HDL kinetics and plasma retinol-binding protein-4 (RBP-4) and adiponectin levels in men with the metabolic syndrome.RESEARCH DESIGN AND METHODS- LDL apolipoprotein (apo)B-100 and HDL apoA-1 kinetics were studied in 35 obese men with the metabolic syndrome at the start and end of a 16-week intervention trial of a hypocaloric, low-fat diet (n = 20) versus a weight maintenance diet (n = 15) using a stable isotope technique and multicompartmental modeling.RESULTS - Consumption of the low-fat diet produced significant reductions (P < 0.01) in BMI, abdominal fat compartments, and homeostasis model assessment score compared with weight maintenance. These were associated with a,significant increase in adiponectin and a fall in plasma RBP-4, triglycerides, LDL cholesterol, and LDL apoB-100 concentration (P < 0.05). Weight loss significantly increased the catabolism of LDL apoB-100 (+27%, P < 0.05) but did not affect production; it also decreased both the catabolic (- 13%) and production (- 13%) rates of HDL apoA-1 (P < 0.05), thereby not altering plasma HDL apoA-1 or HDL cholesterol concentrations. VLDL apoB-100 production fell significantly with weight loss (P < 0.05). The increase in LDL catabolism was inversely correlated with the fall in RBP-4 (r = - 0.54, P < 0.05) and the decrease in HDL catabolism with the rise in adiponectin (r = -0.56, P < 0.01).CONCLUSIONS - in obese men with metabolic syndrome, weight loss with a low-fat diet decreases the plasma LDL apoB-100 concentration by increasing the catabolism of LDL apoB-100; weight loss also delays the catabolism of HDL apoA-1 with a concomitant reduction in the secretion of HDL apoA-1. These effects of weight loss could partly involve changes in RBP-4 and adiponectin levels.