Mechanism of Onset of Hyperphagia in Obese Rats food. In 24 hour fasted lean Zucker rats, the predominant phenotype of VAN was low levels of Y2 expression and high levels of MCH1R and CB1 (Fig. 2); feeding (which releases CCK) increased Y2 expression and decreased MCH1R and CB1 expression (Fig. 2). In fasted obese Zucker rats, expression levels of Y2, CB1 and MCH1R were similar to that observed in fasted lean Zucker rats; however, feeding failed to up-regulate Y2 expression (Fig. 2A, P.0.05), or down-regulate MCH1R expres- sion in VAN (Fig. 2B; p.0.05). CB1 expression was down- regulated in VAN of fasted obese Zucker rats (Fig. 2C; p,0.05), but was still significantly elevated compared to fasted lean Zucker rats (Fig. 2C; p,0.01). Figure 2. Altered CCK induced signaling in obese Zucker rats. Photomicrographs of sections of nodose ganglia to show immunoreactivity for Y2 (A), MCH1R (B), and CB1 (C) from lean and obese Zucker rats fasted 24 hr or refed for 1 hr. A) Y2 expression is elevated by feeding in lean Zucker rats, but not in obese Zucker rats. N = 4. B) MCH1R is decreased by feeding in lean Zucker rats but not in obese Zucker rats. N = 4. C) CB1 is decreased by feeding in lean and obese Zucker rats, but CB1 expression remains significantly higher in fed obese Zucker rats compared to lean Zucker rats. Significant differences were represented as a,b,c between groups. doi:10.1371/journal.pone.0032967.g002 PLoS ONE | www.plosone.org 3 March 2012 | Volume 7 | Issue 3 | e32967