TY - JOUR
T1 - Predicting the murine enterocyte metabolic response to diets that differ in lipid and carbohydrate composition
AU - Sinha, Neeraj
AU - Suarez-Diez, Maria
AU - Van Schothorst, Evert M.
AU - Keijer, Jaap
AU - Martins dos Santos, Vitor
AU - Hooiveld, Guido J.E.J.
PY - 2017/8/18
Y1 - 2017/8/18
N2 - The small intestine serves as gatekeeper at the interface between body and diet and is thought to play an important role in the etiology of obesity and associated metabolic disorders. A computational modelling approach was used to improve our understanding of the metabolic responses of epithelial cells to different diets. A constraint based, mouse-specific enterocyte metabolic model (named mmu-ENT717) was constructed to describe the impact of four fully characterized semi-purified diets, that differed in lipid and carbohydrate composition, on uptake, metabolism, as well as secretion of carbohydrates and lipids. Our simulation results predicted luminal sodium as a limiting factor for active glucose absorption; necessity of apical localization of glucose transporter GLUT2 for absorption of all glucose in the postprandial state; potential for gluconeogenesis in enterocytes; and the requirement of oxygen for the formation of endogenous cholesterol needed for chylomicron formation under luminal cholesterol-free conditions. In addition, for a number of enzymopathies related to intestinal carbohydrate and lipid metabolism it was found that their effects might be ameliorated through dietary interventions. In conclusion, our improved enterocyte-specific model was shown to be a suitable platform to study effects of dietary interventions on enterocyte metabolism, and provided novel and deeper insights into enterocyte metabolism.
AB - The small intestine serves as gatekeeper at the interface between body and diet and is thought to play an important role in the etiology of obesity and associated metabolic disorders. A computational modelling approach was used to improve our understanding of the metabolic responses of epithelial cells to different diets. A constraint based, mouse-specific enterocyte metabolic model (named mmu-ENT717) was constructed to describe the impact of four fully characterized semi-purified diets, that differed in lipid and carbohydrate composition, on uptake, metabolism, as well as secretion of carbohydrates and lipids. Our simulation results predicted luminal sodium as a limiting factor for active glucose absorption; necessity of apical localization of glucose transporter GLUT2 for absorption of all glucose in the postprandial state; potential for gluconeogenesis in enterocytes; and the requirement of oxygen for the formation of endogenous cholesterol needed for chylomicron formation under luminal cholesterol-free conditions. In addition, for a number of enzymopathies related to intestinal carbohydrate and lipid metabolism it was found that their effects might be ameliorated through dietary interventions. In conclusion, our improved enterocyte-specific model was shown to be a suitable platform to study effects of dietary interventions on enterocyte metabolism, and provided novel and deeper insights into enterocyte metabolism.
U2 - 10.1038/s41598-017-07350-1
DO - 10.1038/s41598-017-07350-1
M3 - Article
AN - SCOPUS:85027841008
VL - 7
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
M1 - 8784
ER -