Leptin-based obesity pharmacotherapies were originally developed according to the lipostatic view that elevated circulating leptin levels promote a negative energy balance. A series of independent preclinical findings suggest, however, that a partial reduction in circulating leptin levels (either by immunoneutralization, a peripherally restricted CB1 receptor inverse agonist, or bariatric surgery) can paradoxically lead to weight loss.

中文翻译：

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部分瘦素减少：一种新兴的减肥范式

基于瘦素的肥胖药物疗法最初是根据脂肪抑制观点开发的，即升高的循环瘦素水平会促进负能量平衡。然而，一系列独立的临床前研究结果表明，循环瘦素水平的部分降低（通过免疫中和、外周限制性 CB1 受体反向激动剂或减肥手术）反而会导致体重减轻。