A Semi-physiological Model of Postprandial Triglyceride Response in Lean, Obese and Very obese Subjects Following a high-fat meal

• Published in: Diabetes, obesity & metabolism obesity & metabolism, 2018, Vol.20 (3), p.660
• Main Authors: Leohr, Jennifer, Heathman, Michael, Kjellsson, Maria C.
• Format: Article
• Language: English
• Subjects: body composition; clinical trial; Farmakokinetik och läkemedelsterapi; pharmacodynamics; Pharmacokinetics and Drug Therapy; postprandial; triglycerides; VLDL
• ISSN: 1462-8902; 1463-1326
• DOI: 10.1111/dom.13138

AIMS: To quantify the postprandial triglyceride (TG) response of chylomicrons and very-low-density lipoprotein-V6 (VLDL-V6) after a high-fat meal in lean, obese and very obese healthy individuals, using a mechanistic population lipokinetic modelling 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; only the VLDL-V6 showed a difference across the populations. A turn-over model successfully described the TG concentration-time profiles of both chylomicrons and large VLDL-V6 particles after the high-fat meal. This model consisted of four compartments: two transit compartments for the lag between meal consumption and appearance of TGs in the blood, and one compartment each for the chylomicrons and large VLDL-V6 particles. The rate constants for the production of chylomicrons and elimination of large VLDL-V6 particles, along with the conversion rate of chylomicrons to large VLDL-V6 particles were well defined. CONCLUSIONS: This is the first lipokinetic model to describe the absorption of triglycerides from dietary fats into the blood stream and compares the dynamics of triglycerides in chylomicrons and large VLDL-V6 particles among lean, obese and very obese people. 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.