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 d3-leucine administration using gas chromatography-mass spectrometry. Kinetic parameters were derived using a multicompartmental 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. (J Clin Endocrinol Metab 99: E122-E126, 2014) © Copyright 2014 by The Endocrine Society.