6533b7d8fe1ef96bd1269970

RESEARCH PRODUCT

A computational model of postprandial adipose tissue lipid metabolism derived using human arteriovenous stable isotope tracer data

Marleen A. Van BaakShauna D O'donovanShauna D O'donovanIlja C. W. ArtsNadia J. T. RoumansRoel G. VinkNatal A. W. Van RielNatal A. W. Van RielEdwin C. M. MarimanRalf PeetersMichael LenzMichael LenzTheo M. De Kok

subject

Adipose Tissue/metabolismDIETARY FATTY-ACIDSmedicine.medical_treatmentFatty Acids NonesterifiedBiochemistry0302 clinical medicineEndocrinologyModelsInsulinGlucose/metabolismBiology (General)Organic CompoundsFatty AcidsChemical ReactionsPostprandial Period/physiologyPostprandial PeriodLipidsPostprandialBloodComputational Theory and MathematicsAdipose TissueModeling and SimulationPhysical Sciencesmedicine.medical_specialtyQH301-705.5LipolysisCarbohydratesLIPOPROTEIN-LIPASECarbohydrate metabolism03 medical and health sciencesNEFASDG 3 - Good Health and Well-beingGeneticsLipolysisHumansComputer SimulationMolecular BiologyEcology Evolution Behavior and SystematicsBlood Glucose/metabolismArteriovenous AnastomosisChemical CompoundsBiology and Life SciencesComputational BiologyComputational Biology/methodsmedicine.diseaseLipid MetabolismBiologicalHormonesLipid Metabolism/physiology030104 developmental biologyEndocrinologyBiological TissueGlucoseMOBILIZATION030217 neurology & neurosurgery0301 basic medicineGlycerolBlood GlucosePhysiologyPATHOGENESISAdipose tissueLipids/physiologySDG 3 – Goede gezondheid en welzijnVoeding Metabolisme en GenomicaGlucose MetabolismIsotopesMedicine and Health SciencesMetabolitesINSULIN-RESISTANCEEcologyChemistryHydrolysisMonomersMonosaccharidesArteriovenous Anastomosis/metabolismMetabolism and GenomicsBody FluidsChemistryFatty Acids/metabolismMetabolisme en GenomicaCarbohydrate MetabolismNutrition Metabolism and GenomicsFatty Acids Nonesterified/metabolismAnatomyResearch ArticleInsulin/metabolismINHIBITIONWEIGHT-LOSSModels BiologicalBlood PlasmaMECHANISMSCellular and Molecular NeuroscienceInsulin resistanceVoedingInternal medicinemedicineLife ScienceNonesterified/metabolismNutritionDiabetic EndocrinologyInsulinOrganic ChemistryLipid metabolismECTOPIC FATPolymer ChemistryMetabolism

description

Given the association of disturbances in non-esterified fatty acid (NEFA) metabolism with the development of Type 2 Diabetes and Non-Alcoholic Fatty Liver Disease, computational models of glucose-insulin dynamics have been extended to account for the interplay with NEFA. In this study, we use arteriovenous measurement across the subcutaneous adipose tissue during a mixed meal challenge test to evaluate the performance and underlying assumptions of three existing models of adipose tissue metabolism and construct a new, refined model of adipose tissue metabolism. Our model introduces new terms, explicitly accounting for the conversion of glucose to glyceraldehye-3-phosphate, the postprandial influx of glycerol into the adipose tissue, and several physiologically relevant delays in insulin signalling in order to better describe the measured adipose tissues fluxes. We then applied our refined model to human adipose tissue flux data collected before and after a diet intervention as part of the Yoyo study, to quantify the effects of caloric restriction on postprandial adipose tissue metabolism. Significant increases were observed in the model parameters describing the rate of uptake and release of both glycerol and NEFA. Additionally, decreases in the model’s delay in insulin signalling parameters indicates there is an improvement in adipose tissue insulin sensitivity following caloric restriction.

10.1371/journal.pcbi.1007400https://pure.amc.nl/en/publications/a-computational-model-of-postprandial-adipose-tissue-lipid-metabolism-derived-using-human-arteriovenous-stable-isotope-tracer-data(58f41f00-921f-4060-8ae8-1c6324e318c1).html