Shimizu Yoshiyuki, Son Cheol, Aotani Daisuke, Nomura Hidenari, Hikida Takatoshi, Hosoda Kiminori, Nakao Kazuwa
Medical Innovation Center, Kyoto University Graduate School of Medicine, Kyoto, Japan; Department of Human Health and Science, Kyoto University Graduate School of Medicine, Japan.
Medical Innovation Center, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Neurosci Lett. 2017 Feb 15;640:60-63. doi: 10.1016/j.neulet.2017.01.033. Epub 2017 Jan 14.
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.
瘦素是一种由脂肪细胞产生的厌食激素，它通过下丘脑和包括奖赏系统在内的其他脑区发挥作用。表现出病态肥胖、食欲亢进、胰岛素抵抗和不育的瘦素缺陷型ob/ob小鼠是研究最多的肥胖小鼠模型之一。条件性位置偏爱（CPP）范式是评估底物奖赏价值的标准行为模型。虽然据报道瘦素会降低瘦小鼠对高脂饮食（HFD）的CPP，但在ob/ob小鼠的病理生理条件下，瘦素替代如何影响对HFD的CPP尚不清楚。在本研究中，我们进行了CPP测试，以阐明瘦素对ob/ob小鼠对HFD偏好的影响。与野生型（WT）小鼠相比，ob/ob小鼠在CPP测试中对HFD的偏好显著更高，并且通过瘦素替代，无论体重是否正常化，这种偏好都被抑制到与WT小鼠相当的水平。这些结果表明，瘦素独立于肥胖降低了HFD的奖赏价值，这表明瘦素通过抑制ob/ob小鼠的享乐性进食途径来减少食物摄入。
