High fat diet alters expression of catechol‐O‐methyltransferase in the brains of mice and decreases motivation to obtain reward

Abstract

Obesity is a harmful and costly condition which continues to increase in prevalence. Co‐morbidities accompanying this disease now include brain‐based disorders that impact cognition and mood. Illumina BeadChip Arrays performed on brains from high‐fat diet (HFD) and low‐fat diet (LFD) fed mice revealed a 60‐fold increase in prolactin mRNA expression in HFD mice. Real time PCR confirmed this increase as 1643‐fold. Since central DA inhibits prolactin secretion, the DA degradation enzyme catechol‐O‐methyl transferase (COMT) was examined by real time PCR and showed a 1000‐fold increase HFD mice brains as compared to LFD mice brains. Potentially linked to brain‐based DA loss are behavioral changes such as anhedonia and depression. Saccharin preference testing showed that HFD mice as compared to LFD mice exhibited saccharin aversion (25% vs 75% of total fluid consumption). In support, HFD mice also demonstrated a 2.3‐fold decrease in burrowing as compared to LFD mice. To probe the mechanism of these behavioral changes db/db mice (which lack a functional leptin receptor) were examined and found to have a preference for saccharin (93% vs 27% of total fluid consumption) and increased burrowing (4.5‐fold) when compared to HFD mice. Finally, brain based leptin mRNA expression was increased 3‐fold in HFD mice when compared to LFD mice. Taken together these findings suggest that leptin regulates reward motivation in HFD mice by impacting COMT expression and DA degradation.