Effects of intracerebroventricular injection of rosiglitazone on appetite-associated parameters in chicks

Rosiglitazone, a thiazolidinedione, is a peroxisome proliferator-activated receptor gamma (PPAR-γ) agonist that increases insulin sensitivity. A documented side effect of this diabetes drug is increased appetite, although the mechanism mediating this response is unknown. To better understand effects on food intake regulation, we evaluated the appetite-associated effects of rosiglitazone in an alternative vertebrate and agriculturally-relevant model, the domesticated chick. Four day-old chicks received intracerebroventricular (ICV) injections of 0, 5, 10 or 20 nmol rosiglitazone and food and water intake were measured. Chicks that received 5 and 10 nmol rosiglitazone increased food intake during the 2 h observation period, with no effect on water intake. In the next experiment, chicks were ICV-injected with 10 nmol rosiglitazone and hypothalamus was collected at 1 h post-injection for total RNA isolation. Real-time PCR was performed to measure mRNA abundance of appetite- and glucose regulation-associated factors. Neuropeptide Y (NPY) and proopiomelanocortin (POMC) mRNA decreased while NPY receptor 1 (NPYr1) mRNA increased in rosiglitazone-injected chicks compared to the controls. Results show that central effects of rosiglitazone on appetite are conserved between birds and mammals, and that increases in food intake might be mediated through NPY and POMC neurons in the hypothalamus.