Dipeptidyl-peptidase 4 (DPP4) mediates fatty acid uptake inhibition by glucose via TAS1R3 and GLUT-2 in Caco-2 enterocytes
Verena Preinfalk,
Isabella Kimmeswenger,
Veronika Somoza,
Barbara Lieder
Affiliations
Verena Preinfalk
Christian Doppler Laboratory for Taste Research, Institute of Physiological Chemistry, Faculty of Chemistry, University of Vienna, Vienna, Austria; Vienna Doctoral School in Chemistry (DoSChem), University of Vienna, Vienna, Austria
Isabella Kimmeswenger
Vienna Doctoral School in Chemistry (DoSChem), University of Vienna, Vienna, Austria; Institute of Physiological Chemistry, Faculty of Chemistry, University of Vienna, Vienna, Austria
Veronika Somoza
Institute of Physiological Chemistry, Faculty of Chemistry, University of Vienna, Vienna, Austria; Leibniz Institute for Food Systems Biology at the Technical University of Munich, Freising, Germany
Barbara Lieder
Christian Doppler Laboratory for Taste Research, Institute of Physiological Chemistry, Faculty of Chemistry, University of Vienna, Vienna, Austria; Institute of Physiological Chemistry, Faculty of Chemistry, University of Vienna, Vienna, Austria; Institute of Clinical Nutrition, Department of Human Nutrition and Dietetics, University of Hohenheim, Stuttgart, Germany; Corresponding author. Christian Doppler Laboratory for Taste Research, Institute of Physiological Chemistry, Faculty of Chemistry, University of Vienna, Vienna, Austria.
Both high glucose intake with a high-fat meal and inhibition of dipeptidyl peptidase-4 (DPP4) have been associated with plasma lipid-lowering effects, but mechanistic understanding linking glucose and fat absorption is lacking. We here hypothesized that glucose ameliorates intestinal fatty acid uptake via a pathway involving DPP4. A concentration of 50 mM glucose reduced mean DPP4 activity in differentiated Caco-2 enterocytes by 42.5 % and fatty acid uptake by 66.0 % via nutrient sensing by the sweet taste receptor subunit TAS1R3 and glucose transporter GLUT-2. No effect of the DPP4 substrates GLP-1 and GIP or of the cellular energy status on the reduced uptake of fatty acids was seen, but a direct interaction between DPP4 and fatty acid transporters is suggested. Conclusively we identified DPP4 as a regulator of fatty acid absorption in Caco-2 enterocytes that mediates the inhibition of intestinal fatty acid uptake by glucose via an interplay of GLUT-2 and TAS1R3.
