Antiobesity Effect of a Short-Length Peptide YY Analogue after Continuous Administration in Mice.

ABSTRACT: Gastrointestinal peptides such as peptide YY (PYY) can regulate appetite, which is relevant to the study of obesity. The intraperitoneal bolus administration of PYY_3-36 and a 12-amino acid PYY analogue, benzoyl-[Cha^27,28,36,Aib³¹]PYY_25-36 (1), showed similar anorectic activity by activating the Y2 receptor (Y2R). However, food intake inhibition and body weight loss were not observed upon continuous subcutaneous administration of 1 with osmotic pumps in diet-induced obese (DIO) mice. N-Terminal elongation of 1, together with amino acid substitution at position 24, led to a hydrophilic 14-amino acid peptide, Ac-[d-Hyp²⁴,Cha^27,28,36,Aib³¹]PYY_23-36 (18), that showed higher affinity and more potent agonist activity for Y2R and a robust anorectic activity with potency similar to that of PYY_3-36. In addition, the continuous subcutaneous administration of 18 at 0.3 mg/(kg·day) induced significant body weight loss in DIO mice. These results suggest that a short-length PYY analogue can be a lead compound for antiobesity therapy in a sustained-release formulation.

SUBMITTER: Nishizawa N 

PROVIDER: S-EPMC5467190 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature