Interaction of the GLP-1 and leptin systems on food intake after fasting.

<p>a) 1 and 3 h food intake was suppressed in animals given i3vt GLP-1 and 3h food intake was suppressed by i3vt leptin (*p<0.05 vs. i3vt saline). There was no additive effect of giving GLP-1+ leptin on suppression of food intake in 22h fasted animals. White bar, i3vt saline+i3vt saline; black bar, i3vt saline+i3vt GLP-1; gray bar, i3vt leptin+ i3vt saline; hatched bar, i3vt leptin+i3vt GLP-1. b) 3 h food intake was suppressed by combined IP injections of EX4 and leptin. *p<0.05 in EX4+leptin vs. all other groups at the 3 h time point. White bar, i3vt saline+IP saline; black bar, i3vt saline+IP exendin-4; gray bar, i3vt leptin+IP saline; hatched bar, i3vt leptin+IP exendin-4.</p

Food intake after i3vt GLP-1 or MTII or saline in fed or fasted animals.

<p>a) i3vt GLP-1 suppressed food intake in ad lib (solid bars) fed but not 22 h fasted(hatched bars) animals. *p<0.05 i3vt GLP-1 vs. saline within the ad lib animals; ^#p<0.05 i3vt GLP-1 fasted vs. ad lib fed animals. b) 1 and 3 h food intake was equally suppressed after i3vt melanotan II (MTII) in ad lib fed and fasted for 22 h. *p<0.05 vs. ICV saline in both fed and fasted groups.</p

The impact of glucokinase on the anorexic effect of GLP-1 in fed animals.

<p>a) Food intake was equally suppressed in WT (squares) and GK+/− (circles) mice after IP injection of EX4 (solid symbols) vs. saline (open symbols; *p<0.05 at 4 h after injection). Food intake was also equally suppressed at 4 h by IP GLP-1+vildagliptin in WT (b) and GK+/− (c) mice (*p<0.05 at 4 h post-injection). For b) and c), open circle, IP saline+IP saline; closed circle, IP saline+IP vildagliptin; open square, IP GLP-1+IP saline; closed square, IP GLP-1+IP vildagliptin.</p

The ability of peripherally administered glucose to potentiate the anorexic effect of GLP-1 in fasted animals.

<p>Food intake after a) IP or b) oral glucose prior to an i3vt injection of GLP-1 or saline in fasted rats. Oral, but not IP glucose suppressed food intake after i3vt GLP-1 (*p>0.05 vs. ICV GLP-1+glucose, independent of time). Open bar, IP (a) or oral (b) saline+ i3vt saline; closed bar, IP (a) or oral (b) saline+i3vt GLP-1; gray bar, IP (a) or oral (b) glucose+ i3vt saline; hatched bar, IP (a) or oral (b) glucose+i3vt GLP-1.</p

The impact of blocking CNS glucose metabolism on the anorectic ability of GLP-1 in fed animals.

<p>a) The subthreshold orexigenic dose was assessed in ad lib fed animals after saline (0; white bar), 1 (gray bar), 3 (black bar) or 10 (hatched bar) µg of i3vt 2DG. Food intake was significantly increased by the 10 µg dose over all other doses. The 1 and 3 µg doses had no significant effect on food intake. *p<0.05 i3vt 2DG vs. all other groups. b) Food intake was suppressed after i3vt GLP-1 but not after i3vt GLP-1+2DG in fed animals (*p<0.05 i3vt GLP-1+2DG vs. all other groups). White bar, i3vt saline+ i3vt saline; black bar, i3vt GLP-1+ i3vt saline; gray bar, i3vt saline+ i3vt 2DG; hatched bar, i3vt GLP-1+ i3vt 2DG.</p

The impact of AICAR on GLP-1-induced anorexia.

<p>Animals given CSF+GLP-1 had significantly reduced food intake at 1 and 3 h compared to all other groups (*p<0.05) and AICAR blocked this effect. Open bar, i3vt artificial cerebral spinal fluid+ i3vt saline; closed bar, i3vt artificial cerebral spinal fluid+i3vt GLP-1; gray bar, i3vt AICAR+ i3vt saline; hatched bar, i3vt AICAR+i3vt GLP-1.</p

The ability of i3vt glucose to potentiate the anorexic effect of GLP-1 in fasted animals.

<p>Food intake after i3vt glucose at doses of a) 0.6 µg or b) 540 µg or saline plus GLP-1 or saline in 22 h fasted animals. With both doses of glucose, there was a main effect of drug with animals given GLP-1, regardless of glucose dose, having suppressed food intake (p<0.05; main effect of group). Open bar, i3vt saline+ i3vt saline; closed bar, i3vt saline+i3vt GLP-1; gray bar, i3vt glucose+ i3vt saline; hatched bar, i3vt glucose+i3vt GLP-1.</p