Roux-en-Y gastric bypass (RYGB) is an effective treatment for
obesity. Importantly,
weight loss following RYGB is thought to result in part from changes in brain-mediated regulation of appetite and food intake.
Dopamine (DA) within the dorsal striatum plays an important role in feeding behavior; we therefore hypothesized that RYGB alters DA homeostasis in this subcortical region. In the current study, obese RYGB-operated mice consumed significantly less of a high-fat diet, weighed less by the end of the study, and exhibited lower adiposity than obese
sham-operated mice. Interestingly, both RYGB and
caloric restriction (pair feeding) resulted in elevated DA and reduced
norepinephrine (NE) tissue levels compared with ad libitum fed
sham animals. Consequently, the ratio of NE to DA, a measure of DA turnover, was significantly reduced in both of these groups. The RYGB mice additionally exhibited a significant increase in phosphorylation of
tyrosine hydroxylase at position Ser31, a key regulatory site of DA synthesis. This increase was associated with augmented expression of
extracellular-signal-regulated kinases ERK1/2, the
kinase targeting Ser31. Additionally, RYGB has been shown in animal models and humans to improve
insulin sensitivity and
glycemic control. Curiously, we noted a significant increase in the expression of
insulin receptor-β in RYGB animals in striatum (a glucosensing brain region) compared to
sham ad libitum fed mice. These data demonstrate that RYGB surgery is associated with altered monoamine homeostasis at the level of the dorsal striatum, thus providing a critical foundation for future studies exploring central mechanisms of
weight loss in RYGB.