Feeding response to melanocortin agonist predicts preference for and obesity from a high-fat diet P.C. Chandler * , J.B. Viana, K.D. Oswald, P.K. Wauford, M.M. Boggiano 1 Department of Psychology, Behavioral Neuroscience Division, 415 Campbell Hall, University of Alabama at Birmingham, Birmingham, AL 35294-1170, United States Received 25 February 2005; received in revised form 31 March 2005; accepted 5 April 2005 Abstract Overconsumption and increased selection of high fat (HF) foods contribute to the development of common obesity. Because the hypothalamic melanocortin (MC) system plays an integral role in the regulation of food intake and dietary choice, we tested the hypothesis that proneness (-P) or resistance (-R) to dietary-induced obesity (DIO) may be due to differences in MC function. We found that prior to developing obesity and while still maintained on chow, acute, central administration of MTII, an MC agonist, produced a greater anorectic response in DIO-P rats than in DIO-R rats. However, after only 5 days of exclusive HF feeding, the DIO-R rats had significantly greater suppression of intake after MTII treatment than they did when maintained on chow. In addition, the DIO-P rats were much less responsive to MTII treatment than the DIO-R rats after only 5 days of the HF diet. In fact, MTII-induced anorexia during HF feeding correlated negatively with body weight gained on the HF diet. These results suggest that the voluntary decrease of HF feeding in DIO-R rats may be mediated by increased endogenous MC signaling, a signal likely compromised in DIO-P rats. Differences in MC regulation may also explain the observed preference for HF over a lower fat food choice in DIO-P rats. Finally, the results indicate that responses to exogenous MC challenge can be used to predict proneness or resistance to DIO. D 2005 Elsevier Inc. All rights reserved. Keywords: MTII; Melanotan; Food intake; Body weight; Predictor; Palatable food; Diet choice; Rats; Diet-induced obesity; MC4 receptor; Overeating Environmental factors such as a sedentary lifestyle and the overconsumption of a high fat (HF) diet are frequently cited as causes of common obesity. This is because both factors allow energy intake to exceed energy expenditure. Dietary fat, while not a direct cause of obesity [1–3], induces behavioral and metabolic changes that promote obesity. Specifically, passive overconsumption is more likely to occur with HF food because it is typically very palatable and less satiating than other macronutrients [4,5], and fats contain twice the calories of protein and carbohy- drates per gram. Therefore, in an environment of widely advertised and easily accessible HF food, it may be very difficult for individuals to limit their caloric intake to match their metabolic needs. Furthermore, there is evidence to suggest that while obese individuals have overall greater energy consumption, they also consume a greater proportion of their intake as HF food than do non-obese individuals [6–8]. In addition to increased hedonic and lower satiety properties of HF food that favor overconsumption, thermo- genesis and oxidation of fat are much lower than for other macronutrients, further increasing adipose storage [4,5,9]. There is considerable animal and human data pointing to an important role of the CNS melanocortin (MC) system in the control of energy homeostasis [10–12]. The particular relevance of the MC system to obesity is evident in its role in the selection of dietary fat [13,14], its interaction with other peptides known to promote fat selection [14,15], and in human and animal obesities that are caused by mutations of genes encoding MC receptors (MC-R) and proteins [13,16 – 18]. In these experiments, we examined whether baseline differences in MC function, or differences in MC function 0031-9384/$ - see front matter D 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.physbeh.2005.04.011 * Corresponding author. E-mail address: pchandle@uab.edu (P.C. Chandler). 1 Formerly Mary M. Hagan. Physiology & Behavior 85 (2005) 221 – 230