Laboratory of Molecular and Cellular Endocrinology, Instituto de Investigación Sanitaria (IDIS), Complejo Hospitalario Universitario de Santiago (CHUS) and Santiago de Compostela University (USC), Santiago de Compostela, Spain; CIBER Fisiopatología de la Obesidad y la Nutrición (CIBERobn), Madrid, Spain.
Laboratory of Molecular and Cellular Endocrinology, Instituto de Investigación Sanitaria (IDIS), Complejo Hospitalario Universitario de Santiago (CHUS) and Santiago de Compostela University (USC), Santiago de Compostela, Spain; CIBER Fisiopatología de la Obesidad y la Nutrición (CIBERobn), Madrid, Spain.
Life Sci. 2015 Nov 1;140:57-63. doi: 10.1016/j.lfs.2015.05.003. Epub 2015 May 18.
Leptin is an adipocyte-secreted hormone that inhibits food intake and stimulates energy expenditure through interactions with neuronal pathways in the brain, particularly pathways involving the hypothalamus. Intact functioning of the leptin route is required for body weight and energy homeostasis. Given its function, the discovery of leptin increased expectations for the treatment of obesity. However, most obese individuals and subjects with a predisposition to regain weight after losing it have leptin concentrations than lean individuals, but despite the anorexigenic function of this hormone, appetite is not effectively suppressed in these individuals. This phenomenon has been deemed leptin resistance and could be the result of impairments at a number of levels in the leptin signalling pathway, including reduced access of the hormone to its receptor due to changes in receptor expression or changes in post-receptor signal transduction. Epigenetic regulation of the leptin signalling circuit could be a potential mechanism of leptin function disturbance. This review discusses the molecular mechanisms, particularly the epigenetic regulation mechanisms, involved in leptin resistance associated with obesity and the therapeutic potential of these molecular mechanisms in the battle against the obesity pandemic.
瘦素是一种脂肪细胞分泌的激素，通过与大脑中的神经元通路（特别是涉及下丘脑的通路）相互作用，抑制食欲并刺激能量消耗。瘦素途径的完整功能对于体重和能量平衡是必需的。鉴于其功能，瘦素的发现增加了人们对肥胖治疗的期望。然而，大多数肥胖个体和有体重反弹倾向的个体的瘦素浓度高于瘦个体，但尽管这种激素具有抑制食欲的作用，这些个体的食欲并没有被有效抑制。这种现象被认为是瘦素抵抗，可能是瘦素信号通路中多个水平的损伤导致的，包括由于受体表达的变化或受体后信号转导的变化，导致激素无法进入其受体。瘦素信号通路的表观遗传调控可能是瘦素功能障碍的潜在机制。这篇综述讨论了与肥胖相关的瘦素抵抗所涉及的分子机制，特别是表观遗传调控机制，以及这些分子机制在对抗肥胖流行中的治疗潜力。
