Partial Leptin Reduction as an Insulin Sensitization and Weight Loss Strategy
Partial Leptin Reduction as an Insulin Sensitization and Weight Loss Strategy
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DOI：
10.1016/j.cmet.2019.08.005
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发表时间：
2019-10-01
期刊：
影响因子：
29
通讯作者：
Scherer, Philipp E.
中科院分区：
文献类型：
--
作者：
Zhao, Shangang;Zhu, Yi;Scherer, Philipp E.
瘦素的生理作用被认为是减少食物摄入和增加能量消耗的驱动力。然而，临床上的瘦素疗法未能有效治疗肥胖，主要是由于一种被称为瘦素抵抗的现象。肥胖和相关瘦素抵抗之间的联系机制在很大程度上仍不清楚。通过多种小鼠模型和瘦素中和抗体，我们证明了高瘦素血症是代谢紊乱的驱动力。在肥胖的情况下，血浆瘦素水平的部分降低可以恢复下丘脑瘦素敏感性，有效地减少体重增加并增强胰岛素敏感性。这些结果强调，血浆瘦素水平的部分降低导致瘦素敏感性的改善，同时指出了治疗肥胖及其相关合并症的治疗干预的新途径。
The physiological role of leptin is thought to be a driving force to reduce food intake and increase energy expenditure. However, leptin therapies in the clinic have failed to effectively treat obesity, predominantly due to a phenomenon referred to as leptin resistance. The mechanisms linking obesity and the associated leptin resistance remain largely unclear. With various mouse models and a leptin neutralizing antibody, we demonstrated that hyperleptinemia is a driving force for metabolic disorders. A partial reduction of plasma leptin levels in the context of obesity restores hypothalamic leptin sensitivity and effectively reduces weight gain and enhances insulin sensitivity. These results highlight that a partial reduction in plasma leptin levels leads to improved leptin sensitivity, while pointing to a new avenue for therapeutic interventions in the treatment of obesity and its associated comorbidities.