Laboratory of Molecular Genetics, Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
Albert Einstein College of Medicine, Rose F. Kennedy Center, 1410 Pelham Parkway South, Room 822, Bronx, NY 10461, USA.
Mol Metab. 2013 Dec 5;3(1):73-80. doi: 10.1016/j.molmet.2013.10.007. eCollection 2014 Feb.
Leptin-deficient patients report higher "liking" ratings for food, and leptin replacement therapy normalizes these ratings even before weight loss is achieved. Since animals cannot report their ratings, we studied the relationship between leptin and food reward in leptin-deficient ob/ob mice using a optogenetic assay that quantifies the reward value of sucrose. In this assay, mice chose between one sipper dispensing the artificial sweetener sucralose coupled to optogenetic activation of dopaminergic (DA) neurons, and another sipper dispensing sucrose. We found that the reward value of sucrose was high under a state of leptin deficiency, as well as at a dose of leptin that does not suppress food intake (12.5 ng/h). Treatment with higher doses of leptin decreased the reward value of sucrose before weight loss was achieved (100 ng/h), as seen in leptin-deficient patients. These results phenocopy in mice the behavior of leptin-deficient patients.
瘦素缺乏症患者报告对食物有更高的“喜好”评分，而瘦素替代疗法甚至在体重减轻之前就能使这些评分正常化。由于动物无法报告他们的评分，我们使用一种光遗传测定法研究了瘦素缺乏型 ob/ob 小鼠中瘦素与食物奖励之间的关系，该测定法量化了蔗糖的奖励价值。在该测定法中，小鼠在一个分配人工甜味剂三氯蔗糖并与多巴胺能（DA）神经元光遗传激活偶联的吸管和另一个分配蔗糖的吸管之间进行选择。我们发现，在瘦素缺乏的情况下，以及在不抑制食物摄入的瘦素剂量（12.5ng/h）下，蔗糖的奖励价值很高。用更高剂量的瘦素治疗会在体重减轻之前降低蔗糖的奖励价值（100ng/h），就像瘦素缺乏症患者一样。这些结果在小鼠中模拟了瘦素缺乏症患者的行为。
