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 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.