S 23521 decreases food intake and body weight gain in diet-induced obese rats.

OBJECTIVE: To investigate the effect of S 23521, a new glucagon-like peptide-1-(7-36) amide analogue, on food intake and body weight gain in obese rats, as well as on gene expression of several proteins involved in energy homeostasis. RESEARCH METHODS AND PROCEDURES: Lean and diet-induced obese rats were treated with either S 23521 or vehicle. S 23521 was given either intraperitoneally (10 or 100 microg/kg) or subcutaneously (100 microg/kg) for 14 and 20 days, respectively. Because the low-dose treatment did not affect food intake and body weight, the subcutaneous treatment at high dose was selected to test the effect on selected end-points. RESULTS: Treated obese rats significantly decreased their cumulative energy intake in relation to vehicle-treated counterparts (3401 +/- 65 vs. 3898 +/- 72 kcal/kg per 20 days; p < 0.05). Moreover, their body weight gain was reduced by 110%, adiposity was reduced by 20%, and plasma triglyceride levels were reduced by 38%. The treatment also improved glucose tolerance and insulin sensitivity of obese rats. Regarding gene expression, no changes in uncoupling protein-1, uncoupling protein-3, leptin, resistin, and peroxisome proliferator-activated receptor (PPAR)-gamma were observed. DISCUSSION: S 23521 is an effective glucagon-like peptide-1-(7-36) amide analogue, which induced a decrease in energy intake, body weight, and adiposity in a rat model of diet-induced obesity. In addition, the treatment also improved glucose tolerance and insulin sensitivity of obese rats. These results strongly support S 23521 as a putative molecule for the treatment of obesity.