Role of leptin in conditioned place preference to high-fat diet in leptin-deficient ob/ob mice

Leptin is an adipocyte-derived anorexic hormone that exerts its effects via the hypothalamus and other brain regions, including the reward system. Leptin-deficient ob/ob mice that present morbid obesity, hyperphagia, insulin resistance, and infertility are one of the most investigated mouse models of obesity. Conditioned place preference (CPP) paradigm is a standard behavioral model to evaluate the rewarding value of substrates. While leptin is reported to decrease the CPP of lean mice for high fat diet (HFD), it is unknown how CPP toward HFD is affected by leptin replacement in the pathophysiological condition of ob/ob mice. In the present study, we performed the CPP test in order to clarify the effect of leptin on the preference of ob/ob mice for HFD. Ob/ob mice had a significantly higher HFD preference in CPP test when compared with wild-type (WT) mice and this preference was suppressed to the levels comparable to the WT mice by leptin replacement with or without normalization of body weight. These results demonstrate that leptin decreases the reward value of HFD independently of obesity, suggesting that leptin reduces food intake by suppressing the hedonic feeding pathway in ob/ob mice.