Combined gastrin releasing peptide-29 and glucagon like peptide-1 reduce body weight more than each individual peptide in diet-induced obese male rats

To test the hypothesis that gastrin releasing peptide-29 (GRP-29) combined with glucagon like peptide-1 (7-36) (GLP-1 (7-36)) reduce body weight (BW) more than each of the peptides given individually, we infused the two peptides (0.5 nmol/kg each) in the aorta of free feeding, diet-induced obese (DIO) male Sprague Dawley rats once daily for 25 days and measured BW. We found that GRP-29 and GLP-1 reduce BW, GRP-29 reduced it more than GLP-1 and GRP-29 + GLP-1 reduce BW more than each peptide given alone. This reduction was accompanied by decrease 24-hour food intake (normal rat chow), meal size (MS), duration of first meal and number of meals, and increase latency to the first meal, intermeal interval (IMI) and satiety ratio (IMI/MS, amount of food consumed per a unit of time). Furthermore, the peptides and their combination decreased 24-hour glucose levels. In conclusion, GRP-29 + GLP-1 reduce BW more than each of the peptides given individually.