Effect of level of dysfunction of the melanocortin-4 receptor (MC4R) on overconsumption and binge-like eating of a palatable dessert in mice

Dysfunction of the melanocortin-4 receptor (MC4R) leads to hyperphagia and overweight and has been correlated with obesity and binge-eating in humans. We examined in mice the effect of MC4R dysfunction on development of overconsumption and body weight gain. Wild type (WT) mice, homozygous MC4R knockout (MC4RKO), and carrier (MC4RHET) mice were provided with ad libitum access to moist chow (1:1 powdered Purina 5001 to tap water, 1.67 kcal/g) and daily 8 h access to sugar fat whip (SFW; 2:1 vegetable shortening to sugar, 7.35 kcal/g). MC4RKO mice increased their caloric intake and gained weight. This is indicative of a role of MC4R in maintaining caloric balance and adjusting to the consumption of palatable foods. MC4RHET mice ate similarly to WT mice, which, unlike rats, maintained caloric balance. This suggests that studies of MC4RKO mice may be a more valid model of human overconsumption. We also examined the effect of MC4R dysfunction on binge-like eating patterns in a protocol similar to Corwin's group (Dimitriou et al., 2000). We provided female mice either daily (low restriction, LR) or every-other-day (high restriction, HR) 2 h access to SFW. HR mice of all genotypes showed evidence of binge-like eating, but only MC4RKO mice gained weight. This suggests that a lack of MC4R functioning may not be necessary for the development of binge-like eating, but may be associated with the obesity related to it.