title: The flavanone homoeriodictyol increases SGLT-1-mediated glucose uptake but decreases serotonin release in differentiated Caco-2 cells.
abstract: Flavanoids and related polyphenols, among them hesperitin, have been shown to modulate cellular glucose transport by targeting SGLT-1 and GLUT-2 transport proteins. We aimed to investigate whether homoeriodictyol, which is structurally related to hesperitin, affects glucose uptake in differentiated Caco-2 cells as a model for the intestinal barrier. The results revealed that, in contrast to other polyphenols, the flavanon homoeriodictyol promotes glucose uptake by 29.0 ± 3.83% at a concentration of 100 μM. The glucose uptake stimulating effect was sensitive to phloridzin, but not to phloretin, indicating an involvement of the sodium-coupled glucose transporter SGLT-1, but not of sodium-independent glucose transporters (GLUT). In addition, in contrast to the increased extracellular serotonin levels by stimulation with 500 mM D-(+)-glucose, treatment with 100 μM homoeriodictyol decreased serotonin release by -48.8 ± 7.57% in Caco-2 cells via a phloridzin-sensitive signaling pathway. Extracellular serotonin levels were also reduced by -57.1 ± 5.43% after application of 0.01 μM homoeriodictyol to human neural SH-SY5Y cells. In conclusion, we demonstrate that homoeriodictyol affects both the glucose metabolism and the serotonin system in Caco-2 cells via a SGLT-1-meditated pathway. Furthermore, the results presented here support the usage of Caco-2 cells as a model for peripheral serotonin release. Further investigations may address the value of homoeriodictyol in the treatment of anorexia and malnutrition through the targeting of SGLT-1.
authors.affiliation: Christian Doppler Laboratory for Bioactive Aroma Compounds, Faculty of Chemistry, University of Vienna, Vienna, Austria.|Department for Nutritional and Physiological Chemistry, Faculty of Chemistry, University of Vienna, Vienna, Austria.
authors.forename: Barbara
authors.identifier: http://orcid.org/0000-0002-0527-8330
authors.initials: B
authors.lastname: Lieder
authors.affiliation: Christian Doppler Laboratory for Bioactive Aroma Compounds, Faculty of Chemistry, University of Vienna, Vienna, Austria.
authors.forename: Julia Katharina
authors.initials: JK
authors.lastname: Hoi
authors.affiliation: Department for Nutritional and Physiological Chemistry, Faculty of Chemistry, University of Vienna, Vienna, Austria.
authors.forename: Ann-Katrin
authors.initials: AK
authors.lastname: Holik
authors.affiliation: Symrise AG, Mühlenfeldstraße 1, Holzminden, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Geissler
authors.affiliation: Symrise AG, Mühlenfeldstraße 1, Holzminden, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Hans
authors.affiliation: Christian Doppler Laboratory for Bioactive Aroma Compounds, Faculty of Chemistry, University of Vienna, Vienna, Austria.
authors.forename: Barbara
authors.initials: B
authors.lastname: Friedl
authors.affiliation: Christian Doppler Laboratory for Bioactive Aroma Compounds, Faculty of Chemistry, University of Vienna, Vienna, Austria.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Liszt
authors.affiliation: Symrise AG, Mühlenfeldstraße 1, Holzminden, Germany.
authors.forename: Gerhard E
authors.initials: GE
authors.lastname: Krammer
authors.affiliation: Symrise AG, Mühlenfeldstraße 1, Holzminden, Germany.
authors.forename: Jakob P
authors.initials: JP
authors.lastname: Ley
authors.affiliation: Christian Doppler Laboratory for Bioactive Aroma Compounds, Faculty of Chemistry, University of Vienna, Vienna, Austria.|Department for Nutritional and Physiological Chemistry, Faculty of Chemistry, University of Vienna, Vienna, Austria.
authors.forename: Veronika
authors.initials: V
authors.lastname: Somoza
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D001692:Biological Transport / Q000187:drug effects; D018938:Caco-2 Cells; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000242:Cyclic AMP / Q000378:metabolism; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D047309:Flavones / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D010695:Phlorhizin / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012701:Serotonin / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D051269:Sodium-Glucose Transporter 1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D047309:Flavones; C495674:SLC5A1 protein, human; D051269:Sodium-Glucose Transporter 1; D012701:Serotonin; D010695:Phlorhizin; D000242:Cyclic AMP; C503231:homoeriodictyol; D005947:Glucose