Semi‐physiological model of postprandial triglyceride response in lean, obese and very obese individuals after a high‐fat meal

AIMS To quantify the postprandial triglyceride response of chylomicrons and very low-density lipoprotein-V6 (VLDL-V6) following a high fat meal in lean, obese and very obese healthy subjects, using a mechanistic population lipokinetic modeling approach. METHODS Healthy subjects from three BMI population categories: lean (18.5-24.9), obese (30-33), and very obese (34-40) were enrolled in a clinical study to assess the triglyceride response after a high-fat meal, containing 60% fat. Nonlinear mixed-effect modeling was used to analyze the triglyceride concentrations of chylomicrons and large VLDL-V6 particles. RESULTS The triglycerides in chylomicrons and VLDL-V6 particles had a prominent postprandial peak and represented the majority of the postprandial response. A turn-over model successfully described the triglyceride concentration versus time profiles of both chylomicron and large VLDL-V6 particles post the high fat meal. This model consisted of four compartments: two transit compartments for the lag between meal consumption and appearance of triglycerides in the blood and one compartment for the chylomicron and large VLDL-V6, respectively. The rate constants for the production of chylomicron and elimination of large VLDL-V6 along with the conversion rate of chylomicron to large VLDL-V6 were well defined. CONCLUSIONS This is the first lipokinetic model that describes the absorption of triglycerides from dietary fats into the blood stream and compares the dynamics of triglycerides in chylomicron and large VLDL-V6 among lean, obese and very obese subjects. Such a model can be used to identify where pharmacological therapies act, thereby improving the determination of efficacy, and identifying complementary mechanisms for combinational drug therapies.