The effect of intragastric fructose infusion on homeostatic and hedonic brain regions interacts with the effect of emotional state

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1 The effect of intragastric fructose infusion on homeostatic and hedonic brain regions interacts with the effect of emotional state J. Iven, J.R. Biesiekierski, D. Zhao, J. Tack, L. Van Oudenhove Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Belgium

2 Seventh Annual meeting of the Belgian Nutrition Society April 21 st, 2017 Brussels DISCLOSURE STATEMENT Speaker: Julie Iven The authors have no conflict of interest requiring disclosure in relationship to the presentation.

3 Introduction The brain-gut axis taste, smell, sight, texture vagal afferents gastric distention/ accommodation ghrelin BRAIN-GUT AXIS motilin ACC OFC STR HYP AMY VTA PBN NTS bidirectional neurohumoral communication between gut and brain CCK GLP1 PYY homeostatic hedonic systemic circulation ACC: anterior cingulate cortex AMY: amygdala HYP: hypothalamus NTS: nucleus of the solitary tract OFC: orbitofrontal cortex PBN: parabrachial nucleus STR: striatum VTA: ventral tegmental area Lutter & Nestler, J. Nutr., 2009 Damasio, Nat. Neurosci., 2000 Sam, Neuropharmacology, 2012 Weltens, Zhao & Van Oudenhove, Neurogastroenterol. Motil., 2014

4 Introduction Interoceptive properties - exteroceptive sensory pathways emotional state - fat - fructose? Wasse et al, United European Gastroenterol. J., 2013 subliminal, intragastric fructose N. vagus hypothalamus Rolls, Proc. Nutr. Soc, 2012 Van Oudenhove, jci, 2011

5 Aims & hypothesis Aim investigate if a subliminal, intragastric fructose infusion is able to influence our emotional state Hypothesis attenuated response to sad emotion induction after fructose compared to placebo administration

6 Methods Study visit 25g N = 15 BMI preparation scanner entry leave scanner functional brain imaging Every 10 appetite-related sensations (VAS) Self-Assessment Manikin (SAM) emotion induction

7 Methods Statistical analysis post-infusion VS baseline fructose VS placebo (main effect of nutrient) sad VS neutral emotions (main effect of emotion) nutrient-by-emotion interaction effect appetite-related sensations & emotion scores mixed models pharmacological MRI analysis time course of BOLD signal mask of regions of interest BOLD: blood oxygenation level-dependent

8 Results Hunger No significant differences

9 Results Valence No significant differences

10 Results Arousal No significant differences

11 Results Main effect of nutrient N accumbens amygdala perigenual anterior cingulate cortex anterior insula medulla midbrain pallidum putamen P FWE-corrected.05 at voxel level F-value 2 4 6

12 Results Nutrient-by-emotion interaction effect amygdala N. accumbens hypothalamus anterior insula caudate medulla midbrain pallidum putamen P FWE-corrected.05 at voxel level F-value

13 Results Medulla P.05

14 Results Left anterior insula P.05

15 Results Left orbitofrontal cortex P.05

16 Conclusion behavioural level no effect of emotion induction neural level stronger responses to the fructose administration in the sad emotional state, compared to the neutral emotional state à At the behavioural level, 25g of fructose is not able to provoke a comforting effect, but it does attenuate the brain responses in homeostatic and hedonic brain regions.

17 Acknowledgements Translational Research Center for Gastrointestinal Disorders (TARGID) University of Leuven, Belgium Laboratory for Brain-Gut Axis studies Dr. Jessica Biesiekierski Dongxing Zhao Prof. Jan Tack Prof. Lukas Van Oudenhove

18 Methods Preprocessing imaging data Reorientation T1 Segmentation T1 Normalisation T1 Realignment functional data Slice timing Reorientation functional data Coregistration functional data with T1 Normalisation functional data Smoothing

19 Methods Statistical analysis appetite-related sensations longitudinal data à mixed models planned contrasts to test a priori hypothesis (one-tailed paired T-test) o post-infusion versus baseline o bitter versus placebo hedonic food intake one-tailed paired T-test to test a priori hypothesis

20 Methods Statistical analysis pharmacological MRI analysis time course of BOLD signal o o post-infusion divided in 40 time bins of 1 min each time bin compared to baseline over all time bins (F-test) o o o main effect of fructose main effect of nutrient interaction effect : nutrient by emotion mask of regions of interest BOLD: blood oxygenation level-dependent