美国德克萨斯大学西南医学中心Philipp E. Scherer小组的最新研究表明，部分减少瘦素可作为一种胰岛素增敏和减肥策略。该研究9月5日在线发表于《细胞—代谢》。

通过使用各种小鼠模型和瘦素中和抗体，研究人员证明了高瘦素血症是代谢紊乱的驱动因素。在肥胖的情况下，血浆瘦素水平的部分降低可恢复下丘脑瘦素的敏感性，并有效减少体重增加并增强胰岛素敏感性。这些结果表明，血浆瘦素水平的部分降低导致瘦素敏感性提高，同时为肥胖症及其相关合并症的治疗干预提供了新途径。

据了解，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因素。然而，临床上瘦素疗法未能有效地治疗肥胖症，这主要是由于被称为瘦素抵抗的现象。肥胖与相关的瘦素抵抗之间的联系机制尚不清楚。

附：英文原文

Title: Partial Leptin Reduction as an Insulin Sensitization and Weight Loss Strategy

Author: Shangang Zhao, Yi Zhu, Robbie D. Schultz, Na Li, Zhenyan He, Zhuzhen Zhang, Alexandre Caron, Qingzhang Zhu, Kai Sun, Wei Xiong, Hui Deng, Jia Sun, Yingfeng Deng, Min Kim, Charlotte E. Lee, Ruth Gordillo, Tiemin Liu, Angela K. Odle, Gwen V. Childs, Ningyan Zhang, Christine M. Kusminski, Joel K. Elmquist, Kevin W. Williams, Zhiqiang An, Philipp E. Scherer

Issue&Volume: September 05, 2019

Abstract: 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.

DOI: 10.1016/j.cmet.2019.08.005

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(19)30434-6