Laboratory of Experimental Neurodevelopment, Institute of Development and Paediatric Research (IDIP), La Plata Children's Hospital and Scientific Research Commission, Province of Buenos Aires (CIC-PBA), La Plata, Buenos Aires, Argentina.
Argentine Research Council (CONICET), La Plata, Buenos Aires, Argentina.
J Endocrinol. 2019 Jun 1;241(3):R81-R96. doi: 10.1530/JOE-18-0606.
Leptin resistance refers to states in which leptin fails to promote its anticipated effects, frequently coexisting with hyperleptinaemia. Leptin resistance is closely associated with obesity and also observed in physiological situations such as pregnancy and in seasonal animals. Leptin resensitisation refers to the reversion of leptin-resistant states and is associated with improvement in endocrine and metabolic disturbances commonly observed in obesity and a sustained decrease of plasma leptin levels, possibly below a critical threshold level. In obesity, leptin resensitisation can be achieved with treatments that reduce body adiposity and leptinaemia, or with some pharmacological compounds, while physiological leptin resistance reverts spontaneously. The restoration of leptin sensitivity could be a useful strategy to treat obesity, maintain weight loss and/or reduce the recidivism rate for weight regain after dieting. This review provides an update and discussion about reversion of leptin-resistant states and modulation of the molecular mechanisms involved in each situation.
瘦素抵抗是指瘦素未能发挥预期作用的状态,常伴有高瘦素血症。瘦素抵抗与肥胖密切相关,也可见于妊娠和季节性动物等生理状态。瘦素再敏化是指瘦素抵抗状态的逆转,与肥胖常见的内分泌和代谢紊乱的改善以及血浆瘦素水平的持续下降相关,可能降至临界阈值以下。在肥胖中,通过减少体脂和瘦素的治疗或某些药物化合物可以实现瘦素再敏化,而生理瘦素抵抗则会自发逆转。恢复瘦素敏感性可能是治疗肥胖、维持体重减轻和/或降低节食后体重反弹率的有效策略。本综述提供了关于瘦素抵抗状态逆转和每种情况下涉及的分子机制调节的最新信息和讨论。