Plasma Apolipoprotein B-48 Transport in Obese Men: A New Tracer Kinetic Study in the Postprandial State

Context: The mechanisms responsible for impaired chylomicron metabolism have not been adequately investigated in obese subjects. Objective: We aimed to compare apolipoprotein (apo) B-48 kinetics in obese and lean men by developing a new model to describe the kinetics of apoB-48 particles in the postprandial state. Design, Setting, and Patients: Seven obese and 13 age-matched lean men were given an oral fat load. apoB-48 tracer to tracee ratios were measured after intravenous d(3)-leucine administration using gas chromatography-mass spectrometry. Kinetic parameters were derived using a multi-compartmental model. Outcomes Measures: Plasma total and incremental apoB-48 0-10 hour areas under the curve as well as apoB-48 secretion and fractional catabolic rate. Results: Compared with lean men, fasting plasma triglyceride (+ 148%) and apoB-48 (+ 110%) concentrations as well as plasma total and incremental triglycerides (+ 184% and + 185%, respectively) and apoB-48 (+ 182% and 224%, respectively) areas under the curve were significantly higher in obese men (P < .05 for all). The obese men also had significantly (P < .05 for all) higher secretion rates of apoB-48 in the fasted state (+ 145%) as well as at 3 hours (+ 70%), 4 hours (+ 82%), 5 hours (+ 82%), 6 hours (+ 76%), and 8 hours (+ 61%) in response to the fat load. This was associated with a greater number of apoB-48-containing particles secreted over the 10-hour study period in the obese men, compared with lean men (+ 125%, P < .01). The fractional catabolic rate of apoB-48 was significantly lower in the obese men compared with the lean men (-33%, P < .05) Conclusion: We demonstrate that postprandial hypertriglyceridemia in central obesity relates to an overproduction and impaired catabolism of apoB-48-containing lipoproteins. These findings are based on a new, physiologically relevant, kinetic model, which describes the non-steady-state postprandial metabolism of apoB-48.