In humans, higher cortisol responsiveness during stress is associated with increased food intake. We have identified female sheep that have either high (HR) or low (LR) cortisol responses to Synacthen (adrenocorticotropin: ACTH). When placed on a high energy diet, HR have a greater increase in adiposity than LR, which is not due to different food intake but is associated with a difference in muscle thermogenesis.¹  Hypothalamic appetite-regulating peptides (ARP) exert reciprocal effects on food intake and energy expenditure/ thermogenesis. The aim of this study was to characterise differences in expression and function of ARP in HR and LR ewes. Gene expression for neuropeptide Y (NPY), proopiomelanocortin (POMC), melanin-concentrating hormone (MCH), orexin, MC3R and MC4R was measured by in situ hybridisation (n= 4/group). The expression of ARP genes was similar in HR and LR, but LR showed higher expression of MC3R (P<0.05) and MC4R (P=0.0003). Intracerebroventricular (icv) infusions of a low dose (50µg/h) of NPY, α-melanocyte stimulating hormone (αMSH), orexin and MCH were performed between 1000-1600h in LR and HR ewes (n= 6-7/group) that  were meal-fed (1100-1600h) to entrain a post-prandial thermogenesis. Skeletal muscle and retroperitoneal (RP) fat temperatures were recorded using dataloggers. In muscle, LR animals showed greater (P<0.05) thermogenesis than HR in response to feeding. The temperature response to MCH infusion was lower in LR than in HR, with no effect of NPY, αMSH or orexin infusion. RP fat temperatures in HR and LR were unaffected by ARP infusions. NPY, MCH and orexin did not stimulate food intake in meal-fed HR or LR.αMSH infusion reduced food intake (P<0.01) in the LR group only. With 24h infusions, NPY increased (P<0.001) food intake in both groups but αMSH was only effective in LR (P<0.05). We conclude that increased propensity to obesity in HR may be due to reduced melanocortin signalling²