Fatty acid-induced gut-brain signaling attenuates neural and behavioral effects of sad emotion in humans

Abstract

Although a relationship between emotional state and feeding behavior is known to exist, the interactions between signaling initiated by stimuli in the gut and exteroceptively generated emotions remain incompletely understood. Here, we investigated the interaction between nutrient-induced gut-brain signaling and sad emotion induced by musical and visual cues at the behavioral and neural level in healthy nonobese subjects undergoing functional magnetic resonance imaging. Subjects received an intragastric infusion of fatty acid solution or saline during neutral or sad emotion induction and rated sensations of hunger, fullness, and mood. We found an interaction between fatty acid infusion and emotion induction both in the behavioral readouts (hunger, mood) and at the level of neural activity in multiple pre-hypothesized regions of interest. Specifically, the behavioral and neural responses to sad emotion induction were attenuated by fatty acid infusion. These findings increase our understanding of the interplay among emotions, hunger, food intake, and meal-induced sensations in health, which may have important implications for a wide range of disorders, including obesity, eating disorders, and depression.

Figure 1. Effect of sad emotion and intragastric fatty acid on behavioral ratings.

(A) Hunger. A significant main effect of emotion (increase of hunger during sad, decrease during neutral) and a significant fat-by-emotion interaction (effect of sad on hunger attenuated by fat) was found. **P < 0.01 compared with saline vehicle sad; ***P < 0.001 compared with vehicle sad, corrected for multiple comparisons. (B) Fullness. A significant main effect of emotion (smaller increase in fullness during sad compared with neutral) was found.***P < 0.001 compared with neutral. (C) Mood. A significant main effect of emotion and a significant fat-by-emotion interaction (attenuation of the effect of emotion induction by fat) was found. All pairwise differences were significant after correction for multiple comparisons, except for vehicle neutral compared with fat neutral (NS, P = 0.13). VAS, visual analog scale.

Figure 2. Pre-hypothesized brain ROIs in which a significant fat-by-emotion interaction effect was found.

Analysis thresholded at P_uncorrected < 0.005 for display purposes. HYPOTHAL, hypothalamus; THAL, thalamus; HIPPO, hippocampus.

Figure 3. Average time course (percentage BOLD signal change from baseline per 2-minute time bin) and AUC plots for each condition in selected ROIs.

(A) Right medulla/pons, (B) midbrain/pons, (C) left hypothalamus, (D) right hippocampus, and (E) MCC. *P < 0.05, **P < 0.01, ***P < 0.001, versus fat neutral; ^#P < 0.001, ^##P < 0.01 versus saline sad. A significant fat-by-emotion interaction effect on the BOLD signal was found: fatty acid attenuates the effect of sad emotion compared with saline.