title: Increased colonic propionate reduces anticipatory reward responses in the human striatum to high-energy foods.
abstract: BACKGROUND
  Short-chain fatty acids (SCFAs), metabolites produced through the microbial fermentation of nondigestible dietary components, have key roles in energy homeostasis. Animal research suggests that colon-derived SCFAs modulate feeding behavior via central mechanisms. In humans, increased colonic production of the SCFA propionate acutely reduces energy intake. However, evidence of an effect of colonic propionate on the human brain or reward-based eating behavior is currently unavailable.
  
  
  OBJECTIVE
  We investigated the effect of increased colonic propionate production on brain anticipatory reward responses during food picture evaluation. We hypothesized that elevated colonic propionate would reduce both reward responses and ad libitum energy intake via stimulation of anorexigenic gut hormone secretion.
  
  
  METHODS
  In a randomized crossover design, 20 healthy nonobese men completed a functional magnetic resonance imaging (fMRI) food picture evaluation task after consumption of control inulin or inulin-propionate ester, a unique dietary compound that selectively augments colonic propionate production. The blood oxygen level-dependent (BOLD) signal was measured in a priori brain regions involved in reward processing, including the caudate, nucleus accumbens, amygdala, anterior insula, and orbitofrontal cortex (n = 18 had analyzable fMRI data).
  
  
  RESULTS
  Increasing colonic propionate production reduced BOLD signal during food picture evaluation in the caudate and nucleus accumbens. In the caudate, the reduction in BOLD signal was driven specifically by a lowering of the response to high-energy food. These central effects were partnered with a decrease in subjective appeal of high-energy food pictures and reduced energy intake during an ad libitum meal. These observations were not related to changes in blood peptide YY (PYY), glucagon-like peptide 1 (GLP-1), glucose, or insulin concentrations.
  
  
  CONCLUSIONS
  Our results suggest that colonic propionate production may play an important role in attenuating reward-based eating behavior via striatal pathways, independent of changes in plasma PYY and GLP-1. This trial was registered at clinicaltrials.gov as NCT00750438.
authors.affiliation: Nutrition and Dietetic Research Group, Division of Diabetes, Endocrinology and Metabolism, Faculty of Medicine.
authors.forename: Claire S
authors.initials: CS
authors.lastname: Byrne
authors.affiliation: Nutrition and Dietetic Research Group, Division of Diabetes, Endocrinology and Metabolism, Faculty of Medicine.
authors.forename: Edward S
authors.initials: ES
authors.lastname: Chambers
authors.affiliation: Nutrition and Dietetic Research Group, Division of Diabetes, Endocrinology and Metabolism, Faculty of Medicine.
authors.forename: Habeeb
authors.initials: H
authors.lastname: Alhabeeb
authors.affiliation: Computational, Cognitive and Clinical Neuroimaging Laboratory and.
authors.forename: Navpreet
authors.initials: N
authors.lastname: Chhina
authors.affiliation: Stable Isotope Biochemistry Laboratory, Scottish Universities Environmental Research Centre, University of Glasgow, Glasgow, United Kingdom;
authors.forename: Douglas J
authors.identifier: http://orcid.org/0000-0002-4161-5699
authors.initials: DJ
authors.lastname: Morrison
authors.affiliation: Stable Isotope Biochemistry Laboratory, Scottish Universities Environmental Research Centre, University of Glasgow, Glasgow, United Kingdom;
authors.forename: Tom
authors.initials: T
authors.lastname: Preston
authors.affiliation: School of Science, University of West Scotland, Hamilton, United Kingdom; and.
authors.forename: Catriona
authors.initials: C
authors.lastname: Tedford
authors.affiliation: Clinical Imaging Facility, Imperial College London, Hammersmith Hospital, London, United Kingdom;
authors.forename: Julie
authors.initials: J
authors.lastname: Fitzpatrick
authors.affiliation: Clinical Imaging Facility, Imperial College London, Hammersmith Hospital, London, United Kingdom;
authors.forename: Cherag
authors.initials: C
authors.lastname: Irani
authors.affiliation: Clinical Imaging Facility, Imperial College London, Hammersmith Hospital, London, United Kingdom;
authors.forename: Albert
authors.initials: A
authors.lastname: Busza
authors.affiliation: Department of Surgery and Cancer, Computational and Systems Medicine, Imperial College London, South Kensington Campus, London, United Kingdom.
authors.forename: Isabel
authors.initials: I
authors.lastname: Garcia-Perez
authors.affiliation: Department of Surgery and Cancer, Computational and Systems Medicine, Imperial College London, South Kensington Campus, London, United Kingdom.
authors.forename: Sofia
authors.initials: S
authors.lastname: Fountana
authors.affiliation: Department of Surgery and Cancer, Computational and Systems Medicine, Imperial College London, South Kensington Campus, London, United Kingdom.
authors.forename: Elaine
authors.initials: E
authors.lastname: Holmes
authors.affiliation: Computational, Cognitive and Clinical Neuroimaging Laboratory and Centre for Neuropsychopharmacology, Division of Brain Sciences, and tony.goldstone@imperial.ac.uk g.frost@imperial.ac.uk.
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Goldstone
authors.affiliation: Nutrition and Dietetic Research Group, Division of Diabetes, Endocrinology and Metabolism, Faculty of Medicine, tony.goldstone@imperial.ac.uk g.frost@imperial.ac.uk.
authors.forename: Gary S
authors.initials: GS
authors.lastname: Frost
mesh_terms: D000328:Adult; D059031:Anticipation, Psychological; D001066:Appetite; D001069:Appetite Regulation; D001786:Blood Glucose / Q000378:metabolism; D003106:Colon / Q000378:metabolism*; D003342:Corpus Striatum / Q000378:metabolism*; D018592:Cross-Over Studies; D003463:Cues; D002149:Energy Intake; D005768:Gastrointestinal Hormones / Q000097:blood; D052216:Glucagon-Like Peptide 1 / Q000097:blood; D006801:Humans; D007328:Insulin / Q000097:blood; D007444:Inulin / Q000494:pharmacology; D008297:Male; D062407:Meals; D008875:Middle Aged; D009434:Neural Pathways; D019894:Peptide YY / Q000097:blood; D011422:Propionates / Q000378:metabolism*; D012201:Reward; D012528:Satiety Response
chemical_list: D001786:Blood Glucose; D005768:Gastrointestinal Hormones; D007328:Insulin; D011422:Propionates; D019894:Peptide YY; D052216:Glucagon-Like Peptide 1; D007444:Inulin
keywords: appetite; fMRI; propionate; reward; striatum