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Investigations into the effects of berry flavonoids on nutrient transport processes in Caco-2 enterocytes

Student thesis: Doctoral ThesisDoctor of Philosophy

Flavonoids are known to interact with a number of membrane transporters, influencing the rate of intestinal nutrient absorption. The transcriptional effects and consequences of such interactions remained to be fully elucidated. To address this we carried out gene expression microarray analysis on intestinal Caco-2 cells treated with a flavonoid-rich berry extract (0.125 % w/v for 16 h). This microarray analysis identified alterations in numerous specific nutrient pathways, three of which were selected for further study, namely: 1) glucose, 2) iron and 3) copper. We then determined the effects of berry flavonoids on the expression and function of these transport pathways using qRT-PCR, Western blotting and functional assays.
We found: 1) Chronic treatment (16 h) with flavonoids decreased the expression of glucose transporter genes (GLUT2 and SGLT1) and induced an acute (15 min) inhibitory effect on enterocytic glucose uptake. 2) Chronic treatment (16 h) with berry extract modulated the expression of genes that regulate iron uptake (down-regulation of DMT1, DCYTB and HFE; up-regulation of TfR1). Iron transepithelial transport was decreased by both acute (15 min) and chronic (16 h) berry extract treatment. 3) Chronic berry extract treatment (16 h) decreased the expression of genes that coordinate copper uptake (CTR1, HAH1, ATP7A and ATP7B). However, copper uptake was increased by both acute (15 min) and chronic (16 h) berry extract treatment.
Thus overall, there is a clear effect of flavonoids on the pathways of glucose, iron and copper and a possible interactive effect between these nutrients themselves. Further research into the functional and physiological relevance of our findings will aid in optimising the dietary management of conditions such as diabetes and disturbances in copper or iron homeostasis.
Original languageEnglish
Awarding Institution
Award dateOct 2012

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