Investigation of Human ApoB48 Metabolism Using a New, Integrated Non-steady-state Model of ApoB48 and ApoB100 Kinetics

Background: Triglyceride-rich lipoproteins and their remnants have emerged as major risk factors for cardiovascular disease. New experimental approaches are required that permit simultaneous investigation of the dynamics of chylomicrons (CM) and apoB48 metabolism and of apoB100 in very low-density lipoproteins (VLDL).

Methods: Mass spectrometric techniques were used to determine the masses and tracer enrichments of apoB48 in the CM, VLDL and VLDL density intervals. An integrated non-steady-state multicompartmental model was constructed to describe the metabolism of apoB48- and apoB100-containing lipoproteins following a fat-rich meal, as well as during prolonged fasting.

Results: The kinetic model described the metabolism of apoB48 in CM, VLDL and VLDL . It predicted a low level of basal apoB48 secretion and, during fat absorption, an increment in apoB48 release into not only CM but also directly into VLDL and VLDL . ApoB48 particles with a long residence time were present in VLDL, and in subjects with high plasma triglycerides, these lipoproteins contributed to apoB48 measured during fasting conditions. Basal apoB48 secretion was about 50 mg day , and the increment during absorption was about 230 mg day . The fractional catabolic rates for apoB48 in VLDL and VLDL were substantially lower than for apoB48 in CM.

Discussion: This novel non-steady-state model integrates the metabolic properties of both apoB100 and apoB48 and the kinetics of triglyceride. The model is physiologically relevant and provides insight not only into apoB48 release in the basal and postabsorptive states but also into the contribution of the intestine to VLDL pool size and kinetics.