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Semi-physiological model of postprandial triglyceride response in lean, obese and very obese individuals after a high-fat meal
Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana, USA.
Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana, USA.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.ORCID iD: 0000-0003-3531-9452
2018 (English)In: Diabetes, obesity and metabolism, ISSN 1462-8902, E-ISSN 1463-1326, Vol. 20, no 3, p. 660-666Article in journal (Refereed) Published
Abstract [en]

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: ) were enrolled in a clinical study to assess the TG response after a high-fat meal, containing 60% fat. Non-linear mixed-effect modelling was used to analyse the TG concentrations of chylomicrons and large VLDL-V6 particles.

RESULTS: The TGs 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 TGs from dietary fats into the blood stream and compares the dynamics of TGs 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.

Place, publisher, year, edition, pages
John Wiley & Sons, 2018. Vol. 20, no 3, p. 660-666
Keywords [en]
VLDL, body composition, clinical trial, pharmacodynamics, postprandial, triglycerides
National Category
Endocrinology and Diabetes Pharmaceutical Sciences
Research subject
Pharmacokinetics and Drug Therapy
Identifiers
URN: urn:nbn:se:uu:diva-346128DOI: 10.1111/dom.13138ISI: 000425013600021PubMedID: 29072819OAI: oai:DiVA.org:uu-346128DiVA, id: diva2:1190408
Available from: 2018-03-14 Created: 2018-03-14 Last updated: 2018-04-09Bibliographically approved

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Kjellsson, Maria C.

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