Co-administration of gut hormones suppresses appetite

Neary NM et al. (2005) Peptide YY3–36 and glucagon-like peptide-17–36 inhibit food intake additively. Endocrinology [doi:10.1210/en.2005-0237]

After eating, the levels of the gut hormones glucagon-like peptide 1 (GLP-1) and peptide YY (PYY) are increased. Both hormones inhibit food intake when administered alone; however, the effects of co-administration are unknown.

Neary et al. found that co-administration of synthetic human GLP-1 (GLP-1_7–36) and PYY (PYY_3–36) in lean mice caused a significant reduction in feeding when compared with either hormone alone. A similar effect was observed in genetically obese ob/ob and db/db mice, their wild-type littermates, and in rats feeding in the dark. This result was not the consequence of behavioral changes; however, the number of c-fos-positive neurons in the hypothalamic arcuate nucleus was significantly increased.

They then assessed the effect of co-administration of these synthetic hormones in humans, in a randomized, double-blind, controlled study of 10 healthy volunteers. After an overnight fast, participants received GLP-1_7–36 and PYY_3–36, either alone or in combination. Following infusion, a preweighed buffet meal was served; participants then had unlimited access to food for the next 24 h. Co-administration resulted in a 27% reduction in energy intake at the buffet and cumulative eating was also reduced. Plasma GLP-1 and PYY levels were significantly increased by co-administration of the synthetic hormones. Additionally, 90 min after infusion, fasting insulin levels increased while glucose levels decreased.

The authors conclude that GLP-1_7–36 and PYY_3–36 have additive effects on appetite suppression and propose that co-administration of these hormones might provide a novel therapy for type 2 diabetes.