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 (0.5nmol/kg each) in the aorta of free feeding, diet-induced obese (DIO) male Sprague Dawley rats once daily for 25days 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.

Peptide Tyrosine Tyrosine 3-36 Reduces Meal Size and Activates the Enteric Neurons in Male Sprague-Dawley Rats.

BACKGROUND: Peptide tyrosine tyrosine 3-36 (peptide YY 3-36 or PYY 3-36) reduces food intake by unknown site(s). AIM: To test the hypothesis that the gastrointestinal tract contains sites of action regulating meal size (MS) and intermeal interval (IMI) length by PYY 3-36. METHODS: Peptide YY 3-36 (0, 1, 5, 10 and 20 nmol/kg) was injected in the aorta, the artery that supplies the gastrointestinal tract, prior to the onset of the dark cycle in free feeding male Sprague-Dawley rats and food intake was measured. Then, PYY 3-36 (25 nmol/kg) was injected intraperitoneally in these rats and Fos-like immunoreactivity (Fos-LI, a marker for neuronal activation) was quantified in the small intestinal enteric neurons, both myenteric and submucosal, and the dorsal vagal complex (DVC) of the hindbrain. RESULTS: PYY 3-36 reduced first MS, decreased IMI length, shortened duration of first meal and increased Fos-LI in enteric and DVC neurons. However, PYY 3-36 failed to change the size of the second meal, satiety ratio, latency to first meal, number of meals and 24 h intake relative to saline control. CONCLUSION: The gastrointestinal tract may contain sites of action regulating MS reduction by PYY 3-36.