Low-grade inflammation in obesity causes low-effort food choice.

Inflammation is related to decreased effortful behaviour and altered effort-related responses in several brain regions, such as the dorsomedial prefrontal cortex (dmPFC). While inflammation is prevalent in obesity, its effects on effortful versus more convenient food choices are currently unknown. We investigated the role of low-grade inflammation in effortful food choice behaviour using functional MRI in a cross-sectional study (n = 131 women, BMI > 27 kg/m2) and a 12-week randomized controlled trial investigating the effect of colchicine 0.5 mg/d vs. placebo (n = 49 women, BMI > 30 kg/m2, CRP > 3 mg/l). Effort aversion was measured using a food-related effort-based decision-making task in which participants accepted or rejected offers to exert effort for food rewards. Inflammation (i.e. INFLA-score, a composite score of C-reactive protein, white blood cell count, neutrophil-to-lymphocyte ratio, and platelets) was related to more effort aversion (i.e. a steeper decline in acceptance with increasing effort: OR = 0.27, p = 0.004) and higher effort-related dmPFC signal (β = 0.23, p = 0.025, Rpartial2 = 0.039). Furthermore, inflammation mediated the association between BMI and dmPFC signal. Colchicine treatment decreased systemic inflammation (INFLA-score: β = -0.40 SD, p < 0.001, Rpartial2 = 0.030), increased high-effort choices (OR = 1.32, p = 0.044), and marginally decreased effort-related dmPFC signal (β = -0.51, p = 0.053, Rpartial2 = 0.037) compared to placebo. These findings show a causal role for inflammation in choosing convenience foods in obesity via increased effort aversion and associated dmPFC processing.