Poster Presentation The International Congress of Neuroendocrinology 2014

Low intraperitoneal doses of PYY and GLP-1 reduce appetite without causing feelings of visceral illness in rodents. (#173)

Eleanor Spreckley 1 , Amin Alamshah 1 , Katherine Banks 1 , James Kinsey-Jones 1 , Mohammad Ghatei 1 , Stephen R Bloom 1 , Kevin G Murphy 1
  1. Imperial College London, London, United Kingdom

Obesity is a major global health issue. Current drug treatment options are limited due to efficacy and unacceptable side effect profiles. Understanding the complex neuroendocrine mechanisms that regulate energy homeostasis may facilitate the development of new treatments for obesity. The gut hormones peptide YY (PYY) and glucagon-like peptide 1 (GLP-1) are released post-prandially, resulting in reduced food intake and increased satiety through central and peripheral mechanisms. Physiological levels of PYY and GLP-1 are not usually associated with nausea, whereas high doses of both agents are associated with visceral illness. It is unclear whether nausea represents one end of the satiety spectrum. There may be a threshold dose at which nausea circuits are activated by these peptides. Bolus injections of both PYY and GLP-1 have previously been associated with conditioned taste aversion (CTA), a well-established paradigm used to assess nausea in rodents. We investigated relatively low bolus doses of PYY3-36 (0.75, 2.5, 7.5, 25 nmol/kg) and GLP-17-36 amide (5, 10, 30 nmol/kg). Doses of 2.5, 7.5, 25 nmol/kg of PYY3-36, and 10, 30 nmol/kg of GLP-17-36 amide significantly reduced food intake. Intra-peritoneal administration of low but effective doses of PYY3-36 and GLP-17-36 amide increased plasma levels of these gut hormones compared to fed controls, indicating that these doses were resulting in supraphysiological levels of these hormones. A CTA protocol was then used to determine if the peripheral administration of these doses of PYY or GLP-1 induced feelings of visceral illness. Doses of 7.5 nmol/kg PYY3-36 and 30 nmol/kg GLP-17-36 amide resulted in significant CTA, but lower doses did not. These higher doses may exert their effects on appetite by activating specific nausea circuits. Lower bolus doses of GLP-1 and PYY that do not induce visceral illness may be useful in the treatment of obesity.