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.

Objectives: 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.

Design: 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.

Conclusion: 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.

Keywords: appetite; fMRI; propionate; reward; striatum.

FIGURE 1

Study day protocol. Overview of timings of blood sampling, VAS ratings, breath hydrogen recordings, and scanning protocol. AMV, auditory–motor–visual; IPE, inulin-propionate ester; T1, T1 anatomical scan; VAS, visual analog scale. Adapted from reference with permission.

FIGURE 2

Breath hydrogen concentrations after IPE or control inulin. Values are medians (IQRs), n = 20. The dotted vertical line signifies the time point after which >80% IPE previously has been shown to enter the colon (12). Breath hydrogen concentrations after control inulin (†) or IPE (*) compared with baseline concentrations with the use of paired-samples t tests (calculations performed on normalized data): *^,†P < 0.05, ***^,†††P < 0.005. IPE, inulin-propionate ester; ppm, parts per million.

FIGURE 3

Energy intake at ad libitum meal after IPE or control inulin. Values are mean ± SEM absolute energy intake after control inulin or IPE (paired-samples t test: *P < 0.05, n = 15) (A) and individual percentage differences in energy intake between IPE and control inulin (B). The horizontal solid line in panel B represents the mean 9.5% reduction in energy intake. IPE, inulin-propionate ester.

FIGURE 4

BOLD signal during food evaluation and AMV control fMRI tasks after consumption of IPE or control inulin. Magnitude of the BOLD signal (percentage) in brain reward systems in the caudate (A), nucleus accumbens (B), anterior insula (C), amygdala (D), and OFC (E) during evaluation of pictures of low-ED foods (minus objects contrast) or high-ED foods (minus objects contrast). Bilateral posterior division of superior temporal gyrus in auditory task, left precentral gyrus in motor task, and bilateral lingual gyrus in visual task after control inulin or IPE, n = 18 (F). Results compared with control inulin with the use of 2-factor (A–E) and 1-factor (F) repeated-measures ANCOVA with a post hoc Fisher least-significant difference test while including visit order as a covariate, *P < 0.05; **P < 0.01. AMV, auditory–motor–visual; ED, energy density; IPE, inulin-propionate ester; OFC, orbitofrontal cortex; preCG, precentral gyrus; postSTG, posterior division of superior temporal gyrus.

FIGURE 5

Food picture appeal ratings and rating reaction times after consumption of IPE or control inulin. Magnitude of appeal ratings (1 = not at all; 5 = a lot) (A and B) and reaction times to rate food pictures of varying energy densities as scored with the use of a hand-held button box (C and D) after control inulin or IPE (n = 18). Results given for low-energy or HE foods (A and C) and different categories of HE foods (chocolate, other sweet, and nonsweet savory) (B and D). Results compared with control inulin with the use of 2-factor repeated-measures ANCOVA with post hoc Fisher least-significant difference test while including visit order as a covariate, *P < 0.05; ***P < 0.005. ED, energy density; HE, high-energy; IPE, inulin-propionate ester.