Aerobic exercise reduces high-fat food reward and is associated with altered VTA-NAc pathway activity in mice

This study investigated whether the ventral tegmental area-nucleus accumbens (VTA-NAc) dopaminergic pathway is associated with the effects of aerobic exercise on food reward in high-fat diet (HFD)-fed mice.

Forty-eight male C57BL/6 J mice were randomly assigned to four groups: normal diet control (CG), normal diet with exercise (CEG), high-fat diet control (HG), and high-fat diet with exercise (HEG), with 12 mice per group. The exercise groups underwent moderate-intensity treadmill running (50 min/day, 5 days/week) for 8 weeks. Metabolic parameters, feeding behavior, conditioned place preference (CPP), in vivo electrophysiological activity of the VTA-NAc pathway, and protein expression of tyrosine hydroxylase (TH) and dopamine receptors (D₁​R and D₂​R) were assessed.

Compared to HG mice, HEG mice exhibited significant reductions in body weight, epididymal fat mass, energy intake, and CPP scores for high-fat food. Voluntary locomotion and nighttime energy expenditure were elevated in the exercised group. Electrophysiological analyses revealed that HFD increased local field potential power and medium spiny neuron (MSN) firing frequency in the NAc, which shifted toward control levels after exercise. At the molecular level, HFD downregulated TH and D₂R expression in both VTA and NAc, while aerobic exercise increased these levels and reduced NAc D₁R expression.

Aerobic exercise reduced high-fat food reward, energy intake, and weight gain in HFD-fed mice while improving voluntary activity and energy balance. Preliminary electrophysiological and molecular findings suggest that these behavioral effects may be accompanied by VTA-NAc pathway adaptations; however, the neural findings require confirmation in larger, adequately powered cohorts.